Frederick Augustus Washington Bailey, who later became known as Frederick Douglass, was born a slave in Talbot County, Maryland, near Hillsboro. He was separated from his mother, Harriet Bailey, when he was still an infant. She died when Douglass was about seven. The identity of Douglass' father is obscure: Douglass originally stated that his father was a white man, perhaps his owner, Aaron Anthony; but he later said he knew nothing of his father's identity. At the age of six, Douglass was separated from his grandmother and moved to the Wye House plantation, where Anthony worked as overseer. When Anthony died, Douglass was given to Lucretia Auld, wife of Thomas Auld. Mrs. Auld sent Douglass to Baltimore to serve Thomas' brother, Hugh Auld.

When Douglass was about twelve, Hugh Auld's wife, Sophia, broke the law by teaching him some letters of the alphabet. Thereafter, as detailed in his Narrative of the Life of Frederick Douglass, an American Slave (published in 1845), Douglass succeeded in learning to read from white children in the neighborhood in which he lived, and by observing the writings of the men with whom he worked. When Hugh Auld discovered this, he strongly disapproved, saying that if a slave learned to read, he would become dissatisfied with his condition and desire freedom; Douglass later referred to this as the first anti-abolitionist speech he had ever heard.

As he learned and began to read newspapers, political materials, and books of every description, the young Douglass was exposed to a new realm of thought and experience that led him first to question and then to condemn the institution of slavery itself. In later years, Douglass would credit The Columbian Orator, which he discovered when he was around twelve years old, with clarifying and defining his views of freedom and human rights.

When he was hired out to a Mr. Freeman, Douglass taught slaves how to read the New Testament at a Sabbath school on the plantation. As word spread, the interest among slaves in the local community was extensive enough that on any given week over forty slaves would attend lessons. For about six months, their work went relatively unnoticed. While Freeman himself remained complacent about their activities, other plantation owners became incensed that their slaves had been offered such instruction and burst in one Sunday armed with clubs and stones to disperse the congregation permanently.

In 1833, Thomas Auld took Douglass back from his brother after a dispute ("as a means of punishing Hugh," Douglass wrote).

Dissatisfied with him, Thomas Auld then sent Douglass to work for Edward Covey, a poor farmer who had a reputation as a "slave-breaker," where Douglass was whipped regularly.

Sixteen-year-old Douglass was indeed nearly broken psychologically by his ordeal under Covey, but he finally rebelled against the beatings and fought back. Covey lost in a confrontation with Douglass and never tried to beat him again.

In 1837, Douglass met Anna Murray, a free African American, in Baltimore while he was still enslaved. They were married soon after he obtained his freedom.

In 1836, Douglass first attempted to escape from his owner, Covey. He was unsuccessful. He also tried to escape from Mr. Freeman, a man who hired him out from his owner, Colonel Lloyd. This was his second unsuccessful attempt at escape.

Douglass successfully escaped slavery on September 3, 1838, boarding a train to Havre de Grace, Maryland, dressed in a sailor's uniform and carrying identification papers provided by a free black seaman. After crossing the Susquehanna River by ferry at Havre de Grace, Douglass continued by train to Wilmington, Delaware. From there Douglass went by steamboat to " Quaker City" — Philadelphia, Pennsylvania. His escape to freedom eventually led him to New York, the entire journey taking less than 24 hours. Douglass "officially" won his freedom when British sympathizers paid the slaveholder who legally still owned him.

Douglass joined various organizations in New Bedford, Massachusetts, including a black church, and regularly attended abolitionist meetings. He subscribed to William Lloyd Garrison's weekly journal, The Liberator, and in 1841, he heard Garrison speak at a meeting of the Bristol Anti-Slavery Society. Douglass was unexpectedly asked to speak at one of these meetings, where he told his story and was encouraged to become an anti-slavery lecturer. Douglass was inspired by Garrison, later stating that "no face and form ever impressed me with such sentiments [of the hatred of slavery] as did those of William Lloyd Garrison." Garrison was likewise impressed with Douglass, and wrote of him in The Liberator. Several days later, Douglass delivered his first speech at the Massachusetts Anti-Slavery Society's annual convention in Nantucket. Twenty-three years old at the time, Douglass later said that his legs were shaking. He conquered his nervousness and gave an eloquent speech about his rough life as a slave.

In 1843, Douglass participated in the American Anti-Slavery Society's Hundred Conventions project, a six month tour of meeting halls throughout the Eastern and Midwestern United States. He participated in the Seneca Falls Convention, the birthplace of the American feminist movement, and was a signatory of its Declaration of Sentiments.

In 1851, Douglass merged the North Star with Gerrit Smith's Liberty Party Paper to form Frederick Douglass' Paper, which was published until 1860. Douglass came to agree with Smith and Lysander Spooner that the United States Constitution is an anti-slavery document, reversing his earlier belief that it was pro-slavery, a view he had shared with William Lloyd Garrison. Garrison had publicly demonstrated his opinion of the Constitution by burning copies of it. Douglass' change of position on the Constitution was one of the most notable incidents of a division that emerged in the abolitionist movement after the publication of Spooner's book The Unconstitutionality of Slavery in 1846. This shift in opinion, as well as some other political differences, created a rift between Douglass and Garrison. Douglass further angered Garrison by saying that the Constitution could and should be used as an instrument in the fight against slavery. With this, Douglass began to assert his independence from the Garrisonians. Garrison saw the North Star as being in competition with the National Anti-Slavery Standard and Marius Robinson's Anti-Slavery Bugle.

In March 1860, Annie, Douglass' youngest daughter, died in Rochester, New York, while he was still in England. Douglass returned from England the following month, taking the route through Canada to avoid detection.

By the time of the Civil War, Douglass was one of the most famous black men in the country, known for his oratories on the condition of the black race, and other issues such as women's rights.

Douglass and the abolitionists argued that the aim of the war was to end slavery and that African Americans should be allowed to engage in the fight for their freedom. Douglass wrote about this in his newspapers and gave several speeches declaring his thoughts and how the war was indeed for the liberation of the slaves.

The night of December 31, 1862, when President Lincoln issued the Emancipation Proclamation (which freed the slaves of the Confederacy, while retaining the slaves in Union held areas) Douglass describes the spirit of those waiting for the announcement: "We were waiting and listening as for a bolt from the sky...we were watching...by the dim light of the stars for the dawn of a new day...we were longing for the answer to the agonizing prayers of centuries."

With the North no longer under obligation to return any escaped slaves to the South, Douglass then fought for equality for his people. He and Lincoln worked together providing plans to move the liberated slaves out of the South. Lincoln had doubts about the war ever ending, but soon enough the Confederate forces gave in to the Union and the war for Southern Independence was over.

After the Civil War, Douglass held several important political positions. He served as President of the Reconstruction-era Freedman's Savings Bank; as marshal of the District of Columbia; as minister-resident and consul-general to the Republic of Haiti (1889–1891); and as chargé d'affaires for the Dominican Republic. After two years, he resigned from his ambassadorship because of disagreements with U.S. government policy. In 1872, he moved to Washington, D.C., after his house on South Avenue in Rochester, New York burned down — arson was suspected. Also lost was a complete issue of The North Star.

In 1868, Douglass supported the presidential campaign of Ulysses S. Grant. The Klan Act and the second and third Enforcement Acts were signed into law by President Grant. Grant used their provisions vigorously, suspending habeas corpus in South Carolina and sending troops there and into other states; under his leadership, over 5,000 arrests were made and the Ku Klux Klan was dealt a serious blow. Grant's vigor in disrupting the Klan made him unpopular among many whites, but Frederick Douglass praised him. An associate of Douglass wrote of Grant that African Americans "will ever cherish a grateful remembrance of his name, fame and great services."

In 1872, Douglass became the first African American to receive a nomination for Vice President of the United States, having been nominated to be Victoria Woodhull's running mate on the Equal Rights Party ticket without his knowledge. During the campaign, he neither campaigned for the ticket nor even acknowledged that he had been nominated. Douglass spoke at many schools around the country in the Reconstruction era, including Bates College in Lewiston, Maine in 1873.

At Abraham Lincoln's memorial, Douglass was in the audience while a tribute to Lincoln was being given by a prominent lawyer. The tribute was not as successful as some of the audience there would have hoped. Reluctantly, Douglass was goaded by the people to stand up and speak. At first out of respect for the speaker he declined, but eventually he gave into the pressure and with no preparation gave a fantastic tribute to the President for which he received much respect. The crowd, roused by his speech, gave him a standing ovation. A witness later said, "I have heard Clay speak and many fantastic men, but never have I heard a speech as impressive as that." While this is anecdotal, it is a commonly accepted fact that Lincoln's wife gave Douglass Lincoln's favorite walking stick which still rests in Cedar Lodge. This is both a testimony to the success of Douglass' tribute to Lincoln and also to the effect and influence of his powerful oratory.

Douglass had five children; two of them, Charles and Rossetta, helped produce his newspapers. Douglass was an ordained minister of the African Methodist Episcopal Church.

In 1877, Frederick Douglass purchased his final home in Washington D.C., on the banks of the Anacostia River. He named it Cedar Hill (also spelled CedarHill). He expanded the house from 14 to 21 rooms and included a china closet. One year later, Douglass expanded his property to 15 acres (61,000 m²), with the purchase of adjoining lots. The home is now the location of the Frederick Douglass National Historic Site.

After the disappointments of Reconstruction, many African Americans called Exodusters moved to Kansas to form all-black towns. Douglass spoke out against the movement, urging blacks to stick it out. He was condemned and booed by black audiences.

In 1877, Douglass was appointed a United States Marshal. In 1881, he was appointed Recorder of Deeds for the District of Columbia. His wife (Anna Murray Douglas) died in 1882, leaving him in a state of depression. His association with the activist Ida B. Wells brought meaning back into his life. In 1884, Douglass married Helen Pitts, a white feminist from Honeoye, New York. Pitts was the daughter of Gideon Pitts, Jr., an abolitionist colleague and friend of Douglass. A graduate of Mount Holyoke College (at that time Mount Holyoke Female Seminary), Pitts had worked on a radical feminist publication named Alpha while living in Washington, D.C.. Frederick and Helen Pitts Douglass faced a storm of controversy as a result of their marriage, since she was a white woman and nearly 20 years younger than he. Both families recoiled; hers stopped speaking to her; his was bruised, as they felt his marriage was a repudiation of their mother. But individualist feminist Elizabeth Cady Stanton congratulated the two.

The new couple traveled to England, France, Italy, Egypt and Greece from 1886 to 1887. In later life, Douglass was determined to ascertain his birthday. He adopted Februaury 14th as his birthday because his mother, Harriet Bailey, used to call him her "little valentine". He was born in February of 1817 by his own calculations, but, as described below, historians have found a record indicating his birth in February of 1818.

In 1892 the Haitian government appointed Douglass as its commissioner to the Chicago World's Columbian Exposition. He spoke for Irish Home Rule and on the efforts of Charles Stewart Parnell. He briefly revisited Ireland in 1886.

On February 20, 1895, Douglass attended a meeting of the National Council of Women in Washington, D.C. During that meeting, he was brought to the platform and given a standing ovation by the audience.

Shortly after he returned home, Frederick Douglass died of a massive heart attack or stroke in his adopted hometown of Washington, D.C. He is buried in Mount Hope Cemetery in Rochester, New York.

In 1921, members of the Alpha Phi Alpha Fraternity designated Frederick Douglass as an honorary member of the fraternity. He holds the distinction of being the only member initiated posthumously.