Born in Brooklyn, Lena Horne was determined to become a performer from a very early age, despite her family's objections. She got her first job as a chorus girl at Harlem's Cotton Club when she was only fifteen. One year later, in 1934, she received a small role in an all-black Broadway show, Dance With Your Gods. In 1935 she became the featured singer in Noble Sissle's Society Orhcestra under the name Helena Horne (presumably more glamorous than Lena). After appearing in the film The Duke is Topes in 1938, she returned to New York to sing in Blackbirds of 1939. The show ended after only eight nights.

In 1941 Horne began performing at Café Society Downtown, a club in New York that catered to intellectuals and social activists. She immersed herself in black history and politics, and resumed her friendship with Paul Robeson, who she had known as a child. The next year she became the first black woman since 1915 (the second ever) to sign a term contract with a film studio, when she agreed to a seven year contract with MGM. Once she started making films, however, the studio considered her too light-skinned to play opposite black actors, but was unwilling to feature her with white actors. She also refused to depict negative images of black women. Her film appearances were therefore limited mainly to "specialty sequences," in which she sang, elegantly dressed and leaning provocatively against a pillar, which could be cut when the films were shown in the South. Her major films were the 1943 all-black musicals Cabin in the Sky and Stormy Weather. The song Stormy Weather became her trademark.

In the early 1950s Horne was a target of anti-communist blacklisting, preventing her from working on radio and television. She was blacklisted until 1956, when she was cleared of charges and signed a recording contract with RCA Victor. Her albums, Stormy Weather, Lena Horne at the Coconut Grove, and Lena Horne at the Waldorf-Astoria, were incredibly popular; Lena Horne at the Waldorf-Astoria became the top-selling album by a female artist in RCA's history. In the 1960s she performed on the Ed Sullivan Show, the Perry Como variety show, and hosted her own Lena in Concert. In 1965 she published her autobiography, Lena. Over the next two decades she would appear as Glenda the Good Witch in 1978's The Wiz, launch a farewell tour in 1980, and star in a one-woman show, Lena Horne: The Lady and Her Music, which opened in 1981 to tremendous popular and critical acclaim. She received a Tony Award and Drama Desk Award for the performance. It was the longest-running one-woman show in the history of Broadway; the soundtrack received two Grammy Awards.

Horne's performance style and musical talent are legendary. She is considered a jazz icon and tireless advocate for black actors in Hollywood. A dedicated civil rights activist, she participated in the 1963 March on Washington, performed at numerous civil rights rallies across the country, and worked on behalf of the National Council for Negro Women.