Horne was born in Bradford, Pennsylvania, but moved with her parents to Long Beach, California when she was 11. At the age of 13, she became part of the newly formed Los Angeles Concert Youth Chorus -- whose other members included a 14-year old Marni Nixon and a 19-year old Paul Salamunovich, among many others -- under famed conductor Roger Wagner; this choir evolved into the Roger Wagner Chorale in 1948, and later into the Los Angeles Master Chorale in 1964. She eventually graduated high school from Long Beach Polytechnic High School.
Horne's first major professional engagement was in 1954, when she dubbed the singing voice of Dorothy Dandridge in the film Carmen Jones. Until that point, she had worked as a background singer for several TV sitcoms, as well as recorded covers of popular songs of the early 1950s, which were sold in dimestores around the country for $1.98. She made an appearance on The Odd Couple as a meek and nervous would-be singer, Jackie, who develops into a full-blown diva and essays the role of Carmen with brilliant results; she also sang on The Tonight Show Starring Johnny Carson. She made her Los Angeles debut the same year when she performed the role of Hata in The Bartered Bride with the Los Angeles Guild Opera.
Her first major breakthrough came when her singing ability was recognized by Igor Stravinsky; her operatic career began when he invited her to perform in the 1956 Vienna festival. She remained in Europe for three seasons singing for the Gelsenkirchen Opera.
She was highly acclaimed for her performance as Marie in Alban Berg's Wozzeck at the inauguration of Gelsenkirchen's new opera house on May 22 1960. In 1964, she returned to the United States to appear in Wozzeck at the San Francisco Opera.
For many years, Horne was associated with the Australian soprano Dame Joan Sutherland in their performances of the bel canto repertoire. They first performed together in a concert version of Vincenzo Bellini's Beatrice di Tenda at Carnegie Hall in February 1961. In 1965, they were paired again in a performance of Rossini's Semiramide with the Opera Company of Boston.
Horne made her debut at Covent Garden in October 1964 as Marie in Wozzeck. Her La Scala debut was as Jocasta in Stravinsky's opéra-oratorio, Œdipus rex on March 13 1969. Another of Horne's breakthroughs occurred that same year during a performance of Rossini's Le siège de Corinthe at La Scala, when Horne received a remarkable mid-act seven minute ovation. Horne made her debut at the Metropolitan Opera in 1970 as Adalgisa in Bellini's Norma with Sutherland in the title role. She thereafter appeared regularly at the Met, opening the 1972-1973 season as Carmen. A great success there was in Meyerbeer's Le prophète, in John Dexter's production. In 1984, she sang the title role of Handel's opera seria Rinaldo (directed by Frank Corsaro), the first Handel opera ever performed at the Met.
Although best known for her bel canto and opera seria roles, Horne also performed much American music, both contemporary music, by composers such as William Bolcom, and traditional popular songs. She can be heard on the soundtrack of Flower Drum Song singing "Love, Look Away" and sings the role of Lady Thiang on the Philips recording of The King and I which stars Julie Andrews and Ben Kingsley.
In 1983 she published (with co-writer Jane Scovell) a candid autobiography, My Life, and a continuation volume, Marilyn Horne, The Song Continues, appeared in 2004.
Horne received many honors during her career. A particularly notable one was a New York Times article, penned by then editor of Opera News, Robert Jacobson, in celebration of the Met's 100th anniversary in 1983. Jacobson listed the 100 greatest singers to ever perform at the house. Horne was the only one still actively singing at that time. Horne retired from the concert stage in 1999 with a recital at the Chicago Symphony Center. She still occasionally performs at pop concerts (most recently with cabaret star Barbara Cook), her voice undimmed by age. Horne has also established The Marilyn Horne Foundation to help preserve the art of vocal recitals. She teaches a series of annual Master Classes at the Oberlin Conservatory of Music and the University of Oklahoma.
It was reported in January 2006, shortly after Horne's 72nd birthday, that she had been diagnosed the previous month with localized pancreatic cancer, but her prognosis was good. In January 2007, she appeared at a public function for her Foundation.