Eckstine attended Peabody High School before moving to Washington, DC. He attended Armstrong High School, St. Paul Normal and Industrial School, and Howard University. He left Howard in 1933 after winning first place in an amateur talent contest.

Heading to Chicago, Eckstine joined Earl Hines’ Grand Terrace Orchestra in 1939, staying with the band as vocalist and trumpeter until 1943. By that time, Eckstine had begun to make a name for himself through the Hines band’s juke-box hits such as “Stormy Monday Blues”, and his own “Jelly Jelly.”

He married his first wife, June, in 1942. After their divorce in 1952, he remarried shortly after to actress and model Carolle Drake in 1953, and they remained married until his death. He was the father of four children by his second marriage and two step-children, including Ed Eckstine, a president of Mercury Records; Guy Eckstine, a Columbia and Verve Records A&R executive and record producer; singer Gina Eckstine; and actor Ronnie Eckstine.

In 1944, Eckstine formed his own big band and it became the finishing school for adventurous young musicians who would shape the future of jazz. Included in this group were Dizzy Gillespie, Dexter Gordon, Miles Davis, Art Blakey, Charlie Parker, and Fats Navarro, as well as vocalist Sarah Vaughan. Tadd Dameron, Gil Fuller and Jerry Valentine were among the band’s arrangers. The Billy Eckstine Orchestra is considered to be the first bop big-band, and had Top Ten chart entries that included “A Cottage for Sale” and “Prisoner of Love”. Both were awarded a gold disc by the RIAA.

Eckstine became a solo performer in 1947, with records featuring lush sophisticated orchestrations. Even before folding his band, Eckstine had recorded solo to support it, scoring two million-sellers in 1945 with “Cottage for Sale” and a revival of “Prisoner of Love”. Far more successful than his band recordings, these prefigured Eckstine’s future career. Eckstine would go on to record over a dozen hits during the late 1940s. He signed with the newly established MGM Records, and had immediate hits with revivals of “Everything I Have Is Yours” (1947), Rodgers and Hart’s “Blue Moon” (1948), and Juan Tizol’s “Caravan” (1949).

Eckstine had further success in 1950 with Victor Young’s theme song to “My Foolish Heart,” and the next year with a revival of the 1931 Bing Crosby hit, “I Apologize”.

His 1950 appearance at the Paramount Theatre in New York City drew a larger audience than Frank Sinatra at his Paramount performance.

In 1951, Eckstine performed at the seventh famed Cavalcade of Jazz concert held at Wrigley Field in Los Angeles which was produced by Leon Hefflin, Sr. on July 8. Also featured were Lionel Hampton and his Revue, Percy Mayfield, Jimmy Witherspoon, Joe Liggins’ Honeydrippers and Roy Brown.

Among Eckstine’s recordings of the 1950s was a 1957 duet with Sarah Vaughan, “Passing Strangers”, a minor hit in 1957, but an initial No. 22 success in the UK Singles Chart.

The 1960 Las Vegas live album, No Cover, No Minimum, featured Eckstine taking a few trumpet solos and showcased his nightclub act. He recorded albums for Mercury and Roulette in the early 1960s, and appeared on Motown albums during the mid to late 1960s. After recording sparingly during the 1970s for Al Bell’s Stax/Enterprise imprint, the international touring Eckstine made his last recording, the Grammy-nominated Billy Eckstine Sings with Benny Carter in 1986.

His friend Duke Ellington recalled Eckstine’s artistry in his 1973 autobiography Music is My Mistress:

Dizzy Gillespie, in reflecting on the band in his 1979 autobiography To Be or Not to Bop, gives this perspective: “There was no band that sounded like Billy Eckstine’s. Our attack was strong, and we were playing bebop, the modern style. No other band like this one existed in the world.” In 1946 Eckstine starred as the hero in the musical film Rhythm in a Riff, which also starred Ann Baker and Lucky Millinder.

In 1984 Eckstine recorded his penultimate album, I Am a Singer, arranged and conducted by Angelo DiPippo and featuring Toots Thielemans on harmonica. In November 1986, Eckstine recorded with saxophonist Benny Carter for his 1987 album Billy Eckstine Sings with Benny Carter. Eckstine made his final recordings for Motorcity Records, a label for ex-Motown artists founded by Ian Levine.

Sammy Davis, Jr. made several live appearances and impersonated Eckstine. Eckstine was a pallbearer at Davis’ funeral in 1990.

Eckstine suffered a stroke while performing in Salina, Kansas, in April 1992, and never performed again. Though his speech improved in the hospital, Eckstine had a heart attack, and died a few months later on March 8, 1993, aged 78. Eckstine’s final word was “Basie”.