Born Eleanora Fagan on April 7, 1915, in Philadelphia, Pennsylvania, she took her professional pseudonym from Billie Dove, an actress she admired, and Clarence Holiday, her probable father.

She dropped out of school at age 11 and worked long hours with her mother who had opened a restaurant called the East Side Grill. When the business failed, they moved to Harlem. Their landlady was a woman named Florence Williams, who ran a brothel. Billie's mother went to work for Florence, and within a matter of days after arriving in New York, Billie herself, not yet 14, was forced to earn her keep in Florence's brothel. The house was raided on May 2, 1929, and Holiday was sent to prison, along with her mother.

When she was 17, Billie caught the attention of music producer John Hammond, who arranged for her to make her recording debut with Benny Goodman. She recorded two songs: "Your Mother's Son-in-Law" and "Riffin' the Scotch", the latter of which sold 5,000 copies and became her first hit.

One night before a performance, Holiday burned her hair with a curling iron. Sylvia Sims, a fellow jazz singer, promptly went to a club down the street where the coat check girls were selling flowers. Sims bought a big white gardenia and gave it to Holiday, who wore it that night to cover her burnt hair. She liked wearing the flower so much that she began to put a gardenia in her hair before every performance.

Saxophonist Lester Young gave her the nickname "Lady Day." In return, she called him "Prez," which was her way of saying that she thought he was the greatest.

During Holiday's time touring with Artie Shaw, she was subjected to racial slurs while performing, made to enter and exit buildings through the kitchen rather than the front door, and at times not allowed to sit on the bandstand with the white singers. Although Shaw tried to stand up for her, he was eventually pressured into hiring a white singer alongside her.

The film features Billie as a singing maid and Louis Armstrong as a bandleader, but producers were pressured to lessen Holiday's and Armstrong's roles to avoid the impression that black people created jazz. "They had taken miles of footage of music and scenes," Holiday later said, "but none of it was left in the picture."

"Strange Fruit" protests the lynching of Black Americans, which had reached a peak in the Southern United States at the turn of the 20th century, comparing the victims to the fruit of trees. The song has been called "a declaration of war" and "the beginning of the civil rights movement."

Already a heavy drinker, she was introduced to heroin by her first husband, trombonist Jimmy Monroe, himself an addict. Much of the money she made went to supporting their habits. In 1947, she was arrested for possession and ended up serving 10 months in a federal prison. Her conviction meant her "cabaret card" in New York was revoked and she could no longer perform at any club where liquor was sold.

She released 16 singles that cracked the top 20 that year, including "Carelessly", which was her only number one hit on the pop charts.