Oscar Pettiford was born September 30, 1922, in Okmulgee, Oklahoma, to a musical family: his mother was of Choctaw descent, his father Harry "Doc" Pettiford half Cherokee and half African-American. The family traveled as itinerant musicians before settling in north Minneapolis, where Oscar was one of eleven children who all performed together in the Pettiford family band, singing and dancing before he moved to piano at twelve and then double bass at fourteen. He briefly gave up the instrument in 1941, doubting he could make a living on it, but resumed five months later after encouragement from bassist Milt Hinton, developing an unusually personal style because, in his own words, he "did not like the way people were playing the bass."

Pettiford left Minneapolis in 1942 when Charlie Barnet hired him for the unusual job of playing bass duets alongside Barnet's own bassist, Chubby Jackson, and he broke into wider notice on December 23, 1943, playing on Coleman Hawkins's Signature Records session "The Man I Love"/"Sweet Lorraine," recorded with Hawkins, pianist Eddie Heywood, and drummer Shelly Manne at WOR Studios in New York, one of the earliest recordings to carry bebop's harmonic language onto record. Around the same time Pettiford was a regular at the after-hours jam sessions at Minton's Playhouse alongside Dizzy Gillespie, Thelonious Monk, and Kenny Clarke, and from late 1943 into early 1944 he co-led a quintet with Gillespie at the Onyx Club on 52nd Street, a group jazz historians count among the first working bebop bands to hold a regular engagement. He worked in Duke Ellington's orchestra from 1945 to 1948 and joined Woody Herman's band in 1949; it was during his time with Herman that a broken arm, suffered playing baseball with the band, sidelined him from the bass. Borrowing a cello from a friend and tuning it in fourths an octave above the bass, he taught himself to solo on it during his recovery, made his first cello recordings in 1950, and became jazz's first significant cello soloist, an achievement that stands alongside his bass playing as his most lasting innovation.

Through the 1950s Pettiford worked primarily as a leader, recording a run of albums for Debut, Bethlehem, and ABC-Paramount that showcased both his bass and cello playing: The New Oscar Pettiford Sextet (recorded December 1953, Debut), featuring Charles Mingus on bass while Pettiford played cello; Oscar Pettiford Sextet (1954, French Vogue); Oscar Pettiford (1954, Bethlehem, also billed as the Oscar Pettiford Modern Quintet); Basically Duke (1954, Bethlehem), a tribute to Duke Ellington's book; and Another One (1955, Bethlehem), praised by AllMusic for a "full, lyrical band sound" that folded in Ellington and calypso influences. In 1956 and 1957-58 he led larger ensembles on The Oscar Pettiford Orchestra in Hi-Fi and its sequel, The Oscar Pettiford Orchestra in Hi-Fi Volume Two (the latter produced by Creed Taylor), both for ABC-Paramount, unusual for their use of French horns and harp alongside a conventional big-band brass and reed section and featuring pianist Tommy Flanagan on the first volume. It was also at a 1955 gig with his group at Café Bohemia that Pettiford unknowingly helped launch another career: he let an unknown Florida schoolteacher named Cannonball Adderley sit in on alto saxophone, and Adderley's playing that night made him the talk of the New York jazz scene within weeks.

Pettiford was equally in demand as a sideman across the decade. He played bass on Miles Davis's The Musings of Miles (1955, Prestige) alongside Red Garland and Philly Joe Jones, and on Thelonious Monk's first two Riverside albums, Thelonious Monk Plays Duke Ellington and The Unique Thelonious Monk (1955-56), plus most of Brilliant Corners (1956); a professional falling-out with Monk during that period ended their collaboration, and the two never recorded together again. He also recommended baritone saxophonist Pepper Adams to bandleader Stan Kenton in May 1956, a connection documented in Adams's own JazzProfiles.com profile that put Adams in front of a national audience for the first time.

In 1958 Pettiford relocated to Copenhagen, Denmark, where he recorded for European labels and performed regularly with Scandinavian musicians including guitarist Attila Zoller and with fellow American expatriates Bud Powell and Kenny Clarke. His final studio recordings, made in Copenhagen between August 1959 and July 1960, were released as My Little Cello on Debut. Pettiford died September 8, 1960, at Frederiksberg Hospital in Copenhagen, three weeks short of his 38th birthday; accounts describe the cause as a polio-like viral illness that led to paralysis, a tracheotomy, and fatal complicating pneumonia.

Pettiford is widely regarded as the most important bassist to emerge between Jimmy Blanton and Charles Mingus, translating bebop's harmonic vocabulary and rhythmic drive into horn-like, rapid-fire bass lines and giving the instrument a new solo voice; bassist Christian McBride has called him "probably the most important bass player of that bebop generation in terms of creating new language for the bass." His parallel invention, playing pizzicato and arco cello as a genuine solo instrument rather than a novelty, opened a role in jazz that later bassist-cellists such as Ron Carter would continue. As a composer he left a small but durable body of original tunes, most notably "Tricotism," recorded over the decades by Ray Brown, Milt Hinton, and others, along with "Bohemia After Dark" and "Laverne Walk." His large-ensemble writing for the two ABC-Paramount Hi-Fi albums, built around French horns and harp rather than a standard big-band reed and brass blend, reflected the same restless, orchestrally curious sensibility that ran through his composing and bandleading.