Nina Simone was born Eunice Kathleen Waymon on February 21, 1933, in Tryon, North Carolina, the sixth of eight children. Her father, John Divine Waymon, worked as a barber and dry cleaner and also performed; her mother, Mary Kate Irvin, was a Methodist preacher. She was picking out hymns on the piano at three or four, played in her local church, and gave her first classical recital at twelve. A fund set up by her music teacher and other townspeople paid for her education, and she graduated as valedictorian of Allen High School for Girls in Asheville. In the summer of 1950 she studied at Juilliard with Carl Friedberg to prepare for an audition at the Curtis Institute of Music in Philadelphia. Curtis turned her down. Her family had moved to Philadelphia in expectation of her admission, and she said for the rest of her life that she was rejected because she was Black, a charge the school has denied. She continued with private lessons under Vladimir Sokoloff, a Curtis professor, and worked as an accompanist and piano teacher.

To pay for those lessons she took a job in 1954 playing at the Midtown Bar & Grill in Atlantic City, New Jersey. The owner insisted that she sing as well as play, and she began performing a mix of jazz standards, blues, hymns and classical pieces under a new name, partly so that her mother would not learn she was playing "the devil's music." Nina came from a boyfriend's nickname for her, and Simone from the French actress Simone Signoret. In December 1957 she recorded thirteen or fourteen songs for Bethlehem Records in New York with the bassist Jimmy Bond and the drummer Albert "Tootie" Heath. She sold the rights outright for $3,000 and later lost out on more than a million dollars in royalties. Little Girl Blue came out in February 1959. She had learned George Gershwin's "I Loves You, Porgy" from a Billie Holiday record, and when Bethlehem finally issued it as a single in 1959 it reached No. 18 on the Billboard Hot 100 and No. 2 on the R&B chart. It was her only US top-twenty pop hit.

She signed with Colpix in April 1959, with producer Hecky Krasnow, on terms that left the choice of material to her. The Amazing Nina Simone followed that year. On September 12, 1959 she made her concert debut at Town Hall in New York, billed on a Jazz at Town Hall evening with the quintets of Horace Silver and J.J. Johnson; the Town Hall album was released that December. The Colpix years produced Nina at Newport (1960), Forbidden Fruit (1961), Nina at the Village Gate (1962), the Ellington tribute Nina Simone Sings Ellington (1962) and Nina Simone at Carnegie Hall (1963), the last with the bassist Lisle Atkinson. In New York she became friends with James Baldwin, Langston Hughes and Lorraine Hansberry. In December 1961 she married Andrew Stroud, a New York police detective who became her manager; she later told the BBC that he abused her psychologically and physically.

In 1964 she moved to Philips, and her music took a political turn. Nina Simone in Concert, taken from Carnegie Hall performances in March and April 1964, opened with "Mississippi Goddam," which she wrote in under an hour after the murder of Medgar Evers on June 12, 1963 and the bombing of the 16th Street Baptist Church in Birmingham on September 15, 1963. The single was boycotted in some southern states. She performed at civil rights gatherings, including the Selma to Montgomery marches, recorded "Four Women" (1966), which was banned by New York's WLIB, and sang "Backlash Blues," with words by Langston Hughes, on her first RCA Victor album, Nina Simone Sings the Blues (1967). With Weldon Irvine she turned an unfinished Lorraine Hansberry play title into "To Be Young, Gifted and Black," first released on Black Gold (1970). On April 7, 1968, three days after the assassination of Martin Luther King Jr., she played Westbury Music Fair, dedicated the night to him, and sang "Why? (The King of Love Is Dead)," written by her bassist Gene Taylor; the recording became part of 'Nuff Said!. In 1969 she appeared at the Harlem Cultural Festival, footage of which is in the 2021 film Summer of Soul. Her RCA singles reached Britain: "Ain't Got No, I Got Life" climbed to No. 2 in 1968 and "To Love Somebody" to No. 5 the following year.

She left the United States in 1970, saying that her protest songs had cost her work, and went first to Barbados and then, at the urging of Miriam Makeba, to Liberia. Her daughter Lisa, who joined her there, has said that her mother was physically and mentally abusive during that period, and Lisa later returned to New York to live with her father. Simone later lived in Switzerland, the Netherlands and France. Her last RCA album was It Is Finished (1974), and she made no record again until Creed Taylor, who had seen her perform in 1977, signed her to CTI for Baltimore (1978); she disliked the production, and it did not chart. In the 1980s she was a regular at Ronnie Scott's in London, where she recorded a live album in 1984, and in 1987 her 1958 recording of "My Baby Just Cares for Me" became a European hit after it was used in a Chanel No. 5 television commercial, reaching the UK top five. Her autobiography, I Put a Spell on You, appeared in the early 1990s, and in 1993 she made her last studio album, A Single Woman, for Elektra. She settled near Aix-en-Provence that year.

Her later life was marked by illness and public difficulty. She was diagnosed with bipolar disorder, and in 1995 a shooting incident involving a neighbor's son near her home in France brought a suspended sentence. She had breast cancer for several years and passed away in her sleep at her home in Carry-le-Rouet on April 21, 2003, aged 70. She had learned only days before that the Curtis Institute would award her an honorary degree. Among those at her funeral were Miriam Makeba, Patti LaBelle, Ossie Davis and Ruby Dee, and her ashes were scattered in several African countries. Her daughter, the singer and actress Lisa Simone, was executive producer of the 2015 documentary What Happened, Miss Simone?, which was nominated for an Academy Award. She was inducted into the Rock and Roll Hall of Fame in 2018 and the National Rhythm & Blues Hall of Fame in 2021, and Rolling Stone ranked her No. 21 on its 2023 list of the 200 greatest singers.

Simone was a classically trained pianist who became a singer by accident, and she never studied voice. She told an interviewer in 1970 that she sang everything she heard and picked the key that hid the limits of her range. What she brought from the keyboard was Bach-style counterpoint, the Romantic virtuosity of Chopin, Liszt and Rachmaninoff, and a contralto she used for sustained notes, long silences and spoken asides to the audience. Miles Davis was among the musicians who admired her ability to play three-part counterpoint inside a pop song and improvise on it. Much of her catalogue sits outside jazz proper: folk and gospel songs, Bessie Smith blues, show tunes, protest songs of her own, and pop and rock covers by Bob Dylan, the Beatles, the Bee Gees and Leonard Cohen. A DownBeat reviewer of Forbidden Fruit said plainly that it was not a jazz album. Her jazz credentials are nonetheless real: she learned her breakthrough ballad from Billie Holiday, recorded a full album of Duke Ellington and Billy Strayhorn songs, shared a Town Hall bill with Horace Silver and J.J. Johnson, worked with jazz rhythm sections for most of her career, and returned to jazz clubs and festivals such as Ronnie Scott's and Montreux in her later years. She is best described as a crossover figure whose roots are in jazz, blues and the classical piano, and whose influence reaches well beyond them. Her songs have been recorded by artists from Aretha Franklin, who recorded "To Be Young, Gifted and Black" on her 1972 album Young, Gifted and Black, to singers working in jazz today, among them Nnenna Freelon, who names her as an early influence. Critics have likened Melody Gardot's phrasing to hers. AllMusic's Mark Deming ranked her among the most gifted and the most eclectic singers of her generation.