Clifford Benjamin Brown was born October 30, 1930, in Wilmington, Delaware, into a musical family that sang together as a home vocal quartet. He grew up fascinated by his father's trumpet, started lessons around age 13 with the Wilmington trumpeter and educator Robert "Boysie" Lowery, and by 1948 was already sitting in on the Philadelphia jazz scene, drawing encouragement from Dizzy Gillespie and Charlie Parker. He enrolled as a math major at Delaware State College before transferring in 1949 to Maryland State College on a music scholarship, where he studied composition and arranging and formed a close friendship with two players who would shape the rest of his short career: drummer Max Roach and trumpeter Fats Navarro, who quickly became his musical idol and primary influence. In June 1950 a serious car accident put Brown in the hospital for the better part of a year; Gillespie visited him there and urged him to keep pursuing music professionally. A month after the crash, Navarro died of a drug overdose, at 26.

Brown recovered and returned to work in 1952 as a member of R&B bandleader Chris Powell's group, the Blue Flames, before moving into more overtly jazz circles: touring and recording with pianist Tadd Dameron's group in 1953, and working with drummer Art Blakey. In June 1953, shortly before leaving the country, he cut his Blue Note debut as a leader, New Star on the Horizon, with altoist Gigi Gryce, tenor player Charlie Rouse, pianist John Lewis, bassist Percy Heath, and Blakey on drums. He then toured Europe that summer and fall with Lionel Hampton's orchestra; when Hampton barred his musicians from recording on their own, Brown and Gryce ignored the order and led a run of freelance sessions in Paris and Stockholm, including a well-documented sextet date recorded September 29 and October 8, 1953, with French rhythm players Henri Renaud, Jimmy Gourley, Pierre Michelot, and Jean-Louis Viale. Back in New York in February 1954, Brown recorded live at Birdland with a proto-Jazz Messengers version of Art Blakey's Quintet, alongside Lou Donaldson and Horace Silver, released as A Night at Birdland, Volume 1 and Vol. 2 on Blue Note.

By mid-1954 Brown had formed a new working quintet co-led with Max Roach, with tenor saxophonist Harold Land, pianist Richie Powell, and bassist George Morrow, recording their debut studio album, Clifford Brown and Max Roach, for EmArcy that December. That same year, DownBeat magazine's critics' poll named him its New Star of the Year, and he recorded as a sideman on Sarah Vaughan's self-titled EmArcy album (including "Lullaby of Birdland"). The Quintet followed with Brown and Roach Incorporated and, in January 1955, the ballads-focused Clifford Brown With Strings, arranged and conducted by Neal Hefti; Brown also guested that year on singer Helen Merrill's EmArcy album, arranged by Quincy Jones. Study in Brown, cut later in 1955, is often cited as one of the defining early hard bop records, built around originals such as "Sandu," "Joy Spring," and "Daahoud" that have since become standards. By early 1956 Sonny Rollins had replaced Land in the group, and the Quintet recorded its final studio album, At Basin Street, at Capitol Studios in New York in January and February of that year.

On June 26, 1956, Brown and Richie Powell were being driven from a Philadelphia jam session toward the band's next date in Chicago by Powell's wife, Nancy, so that the exhausted musicians could sleep. Driving at night in the rain on the Pennsylvania Turnpike west of Bedford, she lost control of the car, which left the road; all three were killed instantly. Brown was 25. He is buried in Mt. Zion Cemetery in Wilmington, Delaware. In 1972, DownBeat's critics inducted him into the magazine's Jazz Hall of Fame.

Brown's death was widely felt as one of the great losses in jazz history, in part because his colleagues so consistently described him as a model of discipline rather than only of talent. Sonny Rollins later said Brown "showed me that it was possible to live a good, clean life and still be a good jazz musician," and Lou Donaldson recalled him doing lip and mouth exercises constantly to maintain his technique. Tenor saxophonist Benny Golson, who had recorded alongside Brown in Tadd Dameron's band in 1953, wrote the tribute "I Remember Clifford" the year after his death; it has since become a jazz standard in its own right.

Brown played with a warm, full tone and a virtuosic command of bebop harmony that critics and fellow musicians alike considered nearly technically flawless, qualities he built directly on the example of his primary influence, Fats Navarro, while pushing the vocabulary further and cleaner. Where much of the first generation of bebop trumpet playing prized speed and harmonic daring, Brown paired that same fluency with a melodic clarity and warmth that made his improvisations feel composed even when they were not, and his original tunes ("Joy Spring," "Daahoud," "Sandu") entered the standard jazz repertoire within a few years of his death. Alongside Max Roach's rhythm section, he helped define the hard bop sound of the mid-1950s: a harder-edged, blues- and gospel-inflected reworking of bebop that pointedly rejected drugs and self-destruction as part of the jazz lifestyle, a stance Brown embodied personally as well as musically. His influence on the generation of trumpeters that followed, including Freddie Hubbard, Woody Shaw, and Charles Tolliver, has been cited repeatedly by critics as direct and foundational; more than half a century after his death he continues to be treated as a benchmark for trumpet technique and tone in jazz education.