Rice was born in Birmingham, Alabama, and grew up in the neighborhood of Titusville. She is the only child of Presbyterian minister Reverend John Wesley Rice, Jr., and wife, Angelena Ray. Reverend Rice was a guidance counselor at Ullman High School and minister of Westminster Presbyterian Church, which had been founded by his father. Angelena was a science, music, and oratory teacher at Ullman.

Condoleezza (whose name is derived from the Italian musical expression, Con dolcezza, which means "with sweetness") experienced firsthand the injustices of Birmingham's discriminatory laws and attitudes. She was instructed to walk proudly in public and to use the facilities at home rather than subject herself to the indignity of "colored" facilities in town. As Rice recalls of her parents and their peers, "they refused to allow the limits and injustices of their time to limit our horizons."

However, Rice recalls various times in which she suffered discrimination on account of her race, which included being relegated to a storage room at a department store instead of a regular dressing room, being barred from going to the circus or the local amusement park, being denied hotel rooms, and even being given bad food at restaurants. Also, while Condoleezza was mostly kept by her parents from areas where she might face discrimination, she was very aware of the civil rights struggle and the problems of Jim Crow Birmingham. A neighbor, Juliemma Smith, described how "[Condi] used to call me and say things like, 'Did you see what Bull Connor did today?' She was just a little girl and she did that all the time. I would have to read the newspaper thoroughly because I wouldn’t know what she was going to talk about." Rice herself said of the segregation era: "Those terrible events burned into my consciousness. I missed many days at my segregated school because of the frequent bomb threats."

During the violent days of the Civil Rights Movement, Reverend Rice armed himself and kept guard over the house while Condoleezza practiced the piano inside. According to J.L. Chestnut, Reverend Rice called local civil rights leader Fred Shuttlesworth and his followers "uneducated, misguided Negroes." Also, Reverend Rice instilled in his daughter and students that black people would have to prove themselves worthy of advancement, and would simply have to be "twice as good" to overcome injustices built into the system. Rice said “My parents were very strategic, I was going to be so well prepared, and I was going to do all of these things that were revered in white society so well, that I would be armored somehow from racism. I would be able to confront white society on its own terms.” While the Rices supported the goals of the civil rights movement, they did not agree with the idea of putting their child in harm's way.

Rice was eight when her schoolmate Denise McNair, aged 11, was killed in the bombing of the primarily black Sixteenth Street Baptist Church by white supremacists on September 15, 1963.

Rice states that growing up during racial segregation taught her determination against adversity, and the need to be "twice as good" as non-minorities. Segregation also hardened her stance on the right to bear arms; Rice has said in interviews that if gun registration had been mandatory, her father's weapons would have been confiscated, leaving them defenseless against Ku Klux Klan nightriders.

Rice started learning French, music, figure skating and ballet at age three. At age 15, she began classes with the goal of becoming a concert pianist. Her plans changed when she realized that she did not play well enough to support herself through music alone. While Rice is not a professional pianist, she still practices often and plays with a chamber music group. Rice made use of her pianist training to accompany cellist Yo-Yo Ma for Brahms's Violin Sonata in D Minor at Constitution Hall in April 2002 for the National Medal of Arts Awards.

In 1967, the family moved to Denver, Colorado. She attended St. Mary's Academy, a private all-girls Catholic high school in Cherry Hills Village, Colorado. After studying piano at the Aspen Music Festival and School, Rice enrolled at the University of Denver, where her father both served as an assistant dean and taught a class called "The Black Experience in America." Dean John Rice opposed institutional racism, government oppression, and the Vietnam War.

Rice attended a course on international politics taught by Josef Korbel, the father of future Secretary of State Madeleine Albright. This experience sparked her interest in the Soviet Union and international relations and made her call Korbel "one of the most central figures in my life."

Rice graduated from St. Mary's Academy in 1970. In 1974, at age 19, Rice earned her B.A. in political science, Phi Beta Kappa, from the University of Denver. In 1975, she obtained her Master's Degree in political science from the University of Notre Dame. She first worked in the State Department in 1977, during the Carter administration, as an intern in the Bureau of Educational and Cultural Affairs. In 1981, at the age of 26, she received her Ph.D. in Political Science from the Graduate School of International Studies at Denver. Her dissertation along with some of her earliest publications, centered on military policy and politics in Czechoslovakia.

Rice was a Democrat until 1982 when she changed her political affiliation to Republican after growing averse to former President Jimmy Carter's foreign policy. She also cited influence from her father, John Wesley, in this decision, who himself switched from Democrat to Republican after being denied voting registration by the Democratic registrar. In her words to the 2000 Republican National Convention, "My father joined our party because the Democrats in Jim Crow Alabama of 1952 would not register him to vote. The Republicans did."

However, despite her party switch, Rice served as foreign policy advisor to the presidential campaign of Democratic U.S. Senator Gary Hart of Colorado during the 1984 primaries.

Rice was hired by Stanford University as an Assistant Professor in Political Science (1981–1987). She was granted tenure and promoted, first to Associate Professor (1987–1993), and then to Provost, the chief budget and academic officer of the university (1993–1999), and full Professor (1993–present). Rice was the first female, first minority, and youngest Provost at Stanford. She was also named a Senior Fellow of the Institute for International Studies, and a Senior Fellow (by courtesy) of the Hoover Institution. She was a specialist on the former Soviet Union and gave lectures on the subject for the Berkeley-Stanford joint program led by UC Berkeley Professor George Breslauer in the mid-1980s.

Former Stanford President Gerhard Casper said the university was "most fortunate in persuading someone of Professor Rice's exceptional talents and proven ability in critical situations to take on this task. Everything she has done, she has done well; I have every confidence that she will continue that record as provost." Rice’s Stanford appointment was considered, by Casper, an effort to address concerns about alleged bias at Stanford University. Casper told the New Yorker in 2002 that it “would be disingenuous for me to say that the fact that she was a woman, the fact that she was black … weren't in my mind."

As Stanford's Provost, Rice was responsible for managing the university's multi-billion dollar budget. The school at that time was running a deficit of $20 million. When Rice took office, she promised that the budget deficit would be balanced within "two years." Coit Blacker, Stanford's deputy director of the Institute for International Studies, said there "was a sort of conventional wisdom that said it couldn't be done ... that [the deficit] was structural, that we just had to live with it." Two years later, Rice announced that the deficit been eliminated and the university was holding a record surplus of over $14.5 million.

Rice drew protests when, as provost, she departed from the practice of applying affirmative action to tenure decisions and unsuccessfully sought to consolidate the university's ethnic community centers.

In 1986, while an international affairs fellow of the Council on Foreign Relations, Rice served as Special Assistant to the Director of the Joint Chiefs of Staff.

From 1989 through March 1991 (the period of the fall of Berlin Wall and the final days of the Soviet Union), she served in President George H.W. Bush's administration as Director, and then Senior Director, of Soviet and East European Affairs in the National Security Council, and a Special Assistant to the President for National Security Affairs. In this position, Rice helped develop Bush's and Secretary of State James Baker's policies in favor of German reunification. She impressed Bush, who later introduced her to Soviet leader Mikhail Gorbachev as the one who "tells me everything I know about the Soviet Union."

In 1991, Rice returned to her teaching position at Stanford, although she continued to serve as a consultant on the former Soviet Bloc for numerous clients in both the public and private sectors. Late that year, California Governor Pete Wilson appointed her to a bipartisan committee that had been formed to draw new state legislative and congressional districts in the state.

In 1997, she sat on the Federal Advisory Committee on Gender-Integrated Training in the Military.

During George W. Bush's 2000 U.S. Presidential election campaign, Rice took a one-year leave of absence from Stanford University to help work as his foreign policy advisor. The group of advisors she led called itself The Vulcans in honor of the monumental Vulcan statue, which sits on a hill overlooking her hometown of Birmingham, Alabama. Rice would later go on to give a noteworthy speech at the 2000 Republican National Convention. The speech asserted that “… America's armed forces are not a global police force. They are not the world's 911.”

On December 17, 2000, Rice was picked to serve as National Security Advisor and stepped down from her position at Stanford. She was the first woman to occupy the post. Rice earned the nickname of “Warrior Princess,” reflecting strong nerve and delicate manners.

During the summer of 2001, Rice met with CIA Director George Tenet on an almost daily basis to discuss the possibilities and prevention of terrorist attacks on American targets. Notably, on July 10, 2001, Rice met with Tenet in what he referred to as an "emergency meeting" held at the White House at Tenet's request to brief Rice and the NSC staff about the potential threat of an al Qaeda attack. Rice responded by asking Tenet to give a presentation on the matter to Secretary Rumsfeld and (now-former) Attorney General John Ashcroft.

When asked about the meeting in 2006, Rice asserted she did not recall the specific meeting, commenting that she had met repeatedly with Tenet that summer about terrorist threats. Moreover, she stated that it was "incomprehensible” to her that she ignored terrorist threats two months before the September 11 attacks.

Rice was an outspoken proponent of the 2003 invasion of Iraq. After Iraq delivered its declaration of weapons of mass destruction to the United Nations on December 8, 2002, Rice wrote an editorial for The New York Times entitled Why We Know Iraq Is Lying.

In March 2004, Rice declined to testify before the National Commission on Terrorist Attacks Upon the United States (the 9/11 Commission). The White House claimed executive privilege under constitutional separation of powers and cited past tradition. Under pressure, Bush agreed to allow her to testify so long as it did not create a precedent of Presidential staff being required to appear before United States Congress when so requested. Her appearance before the commission on April 8, 2004, was accepted by the Bush administration in part because she was not appearing directly before Congress. She thus became the first sitting National Security Advisor to testify on matters of policy. In April 2007, Rice rejected, on grounds of executive privilege, a House subpoena regarding the prewar claim that Iraq sought yellowcake uranium from Niger.

Leading up to the 2004 U.S. Presidential election, Rice became the first National Security Advisor to campaign for an incumbent president. She stated that while: "Saddam Hussein had nothing to do with the actual attacks on America, Saddam Hussein's Iraq was a part of the Middle East that was festering and unstable, [and] was part of the circumstances that created the problem on September 11."

On January 18, 2003, the Washington Post reported that Rice was involved in crafting Bush's position on race-based preferences. Rice has stated that "while race-neutral means are preferable," race can be taken into account as "one factor among others" in university admissions policies.

In a January 10, 2003 interview with CNN's Wolf Blitzer, Rice made headlines by stating regarding Iraqi WMD: "The problem here is that there will always be some uncertainty about how quickly he can acquire nuclear weapons. But we don't want the smoking gun to be a mushroom cloud."

After the invasion, when Iraq turned out to have no WMD capability, critics called Rice's claims a "hoax," "deception" and "demagogic scare tactic." "Either she missed or overlooked numerous warnings from intelligence agencies seeking to put caveats on claims about Iraq's nuclear weapons program, or she made public claims that she knew to be false," wrote Dana Milbank and Mike Allen in the Washington Post.

Rice characterized the August 6, 2001 President’s Daily Brief, “Bin Laden to Strike in US" historical information. Rice indicated “It was information based on old reporting.” Sean Wilentz of Salon magazine suggested that the PDB contained current information based on continuing investigations, including that Bin Laden wanted to “bring the fighting to America".

On November 16, 2004, Bush nominated Rice to be Secretary of State. On January 26, 2005, the Senate confirmed her nomination by a vote of 85-13. The negative votes, the most cast against any nomination for Secretary of State since 1825, came from Senators who, according to Boxer, wanted "to hold Dr. Rice and the Bush administration accountable for their failures in Iraq and in the war on terrorism." Their reasoning was that Rice had acted irresponsibly in equating Hussein's regime with Islamist terrorism and some could not accept her previous record. Senator Robert Byrd voted against Rice’s appointment, indicating that she “has asserted that the President holds far more of the war power than the Constitution grants him.”

On October 30, 2005, Rice attended a memorial service in Montgomery, Alabama, in Rice's home state, for Rosa Parks, an inspiration for the American Civil Rights Movement. Rice stated, that she and others who grew up in Alabama during the height of Parks' activism might not have realized her impact on their lives at the time, "but I can honestly say that without Mrs. Parks, I probably would not be standing here today as secretary of state."

As of December 10, 2007 Secretary Rice has visited 66 countries with a total 698,591 miles and 1478.05 hours (61.59 days) of time.

On October 1, 2007, Rice told children (at New York's Public School No. 154, the Harriet Tubman Learning Center) that she would not run for president, slept for 6 1/2 hours a night and was not afraid of war zones. Asked how it felt "to be a lady with such a powerful job", she said: "Sometimes you don't feel all that powerful." Rangel teasingly suggested Rice aim for the White House.

Rice's ratings saw decreases following a heated battle for her confirmation as Secretary of State and following Hurricane Katrina in August 2005. Rice's rise within the George W. Bush administration initially drew a largely positive response from many in the black community. In a 2002 survey, then National Security Advisor Rice was viewed favorably by 41% of black respondents, but another 40% did not know Rice well enough to rate her and her profile remained comparatively obscure. As her role increased, some black commentators began to express doubts concerning Rice's stances and statements on various issues. In 2005, Washington Post columnist Eugene Robinson asked, "How did [Rice] come to a worldview so radically different from that of most black Americans?"

Other writers have also noted what they perceive to be a distance between Rice and the black community. The Black Commentator magazine described sentiments given in a speech by Rice at a black gathering as "more than strange — they were evidence of profound personal disorientation. A black woman who doesn’t know how to talk to black people is of limited political use to an administration that has few black allies." When Rice invoked the civil rights movement to clarify her position on the invasion of Iraq, Margaret Kimberley, another writer for The Black Commentator, felt that her use of the rhetoric was "offensive." Stan Correy, an interviewer from the Australian Broadcasting Corporation, characterized many blacks involved with civil rights and politics as viewing this rhetoric as "cynical." Rice was also described by Bill Fletcher, Jr., the former leader of the TransAfrica Forum, a foreign policy lobbying organization in Washington, D.C., as "very cold and distant and only black by accident." In August 2005, American musician, actor, and social activist Harry Belafonte, who serves on the Board of TransAfrica, referred to blacks in the Bush administration as "black tyrants." Belafonte's comments received mixed reactions.

Rice has defended herself from such criticisms on several occasions. During a September 14, 2005 interview, she said, "Why would I worry about something like that? ... The fact of the matter is I've been black all my life. Nobody needs to tell me how to be black."

A few notable black persons have defended Rice from across the aisle, including Mike Espy, Andrew Young, C. Delores Tucker (chair of the National Congress of Black Women), Clarence Page, Colbert King, Dorothy Height (chair and president emerita of the National Council of Negro Women) and Kweisi Mfume (former Congressman and former CEO of the NAACP).