Bulee "Slim" Gaillard's birth date and birthplace are both disputed, and he encouraged the confusion. The Social Security Death Index gives January 9, 1911, the date used here. Many sources place his birth in Detroit, while Gaillard himself said he was born in Santa Clara, Cuba, to an Afro-Cuban mother and a German-Jewish father who worked as a ship's steward. By his own telling he was left behind on Crete at about twelve during a voyage with his father, spent several years in the eastern Mediterranean picking up Greek and Arabic, and reached Detroit at around fifteen without a word of English. There he worked in an Armenian family's store, tried boxing, and, he said, drove whiskey for the Purple Gang in a hearse during Prohibition. He taught himself guitar and piano, took evening music classes, and went backstage to meet his hero Duke Ellington when the band came through town.

In New York he worked the amateur-night circuit as a tap dancer, guitarist and boogie-woogie pianist, then teamed up in 1936 with the bassist Slam Stewart. As Slim & Slam they played the radio and the clubs of 52nd Street, picked up the manager Martin Block, and signed with Vocalion. On February 17, 1938 they recorded "Flat Foot Floogie (with a Floy Floy)" (Vocalion 4021), credited to Gaillard, Stewart and the songwriter Bud Green. It reached No. 2 on the Billboard chart, and within months it had been covered by Benny Goodman, Louis Armstrong with the Mills Brothers and Fats Waller, among others. The duo's other 1938 records included "Tutti Frutti" and "Laughin' in Rhythm," and they appeared in the 1941 film Hellzapoppin'. The young Los Angeles drummer Chico Hamilton played on Gaillard's recording of "African Jive" in Hollywood in July 1941.

Gaillard was drafted into the Army Air Forces in December 1942, served as an assistant crew chief on B-26 bombers at Laughlin Army Air Field in Texas, and was discharged in 1944 after a diagnosis of chronic sinusitis. He settled in Los Angeles and built a new act around the bassist Bam Brown, recording the hipster anthem "Opera in Vout (Groove Juice Symphony)" and, in the mid-1940s, the novelty hit "Cement Mixer (Put-Ti-Put-Ti)." The pair appeared on the first Cavalcade of Jazz bill at Wrigley Field on September 23, 1945, which also included Count Basie. A quartet with the pianist Dodo Marmarosa and the drummer Zutty Singleton recorded steadily that year. On December 29, 1945 he led a session in Hollywood for Bel-Tone Records with Charlie Parker on alto saxophone and Dizzy Gillespie on trumpet, alongside Jack McVea on tenor, Marmarosa, Brown and Singleton. "Slim's Jam" from that date preserves one of the earliest known recordings of Parker's speaking voice. When Bel-Tone folded, Majestic acquired the masters, and Savoy later reissued them.

Through the late 1940s and early 1950s he was a nightclub headliner, a film novelty (the 1947 featurette O'Voutie O'Rooney was shot at one of his club shows) and a regular opening act at Birdland for Parker, Flip Phillips and Coleman Hawkins. In 1949 he was working in San Francisco, and an account of seeing him perform there appears near the end of Part Two of Jack Kerouac's On the Road (1957), which also celebrates one of his nonsense-syllable improvisations. In 1951 and 1952 he recorded the sessions that became the albums Mish Mash (Mercury, 1953) and Slim Gaillard Cavorts (Clef, 1953), with Dick Hyman on piano on part of the first and Buddy Tate, and later Ben Webster, on tenor saxophone. He took part in Norman Granz's Jazz at the Philharmonic in 1953, and Verve issued the twenty-track Smorgasbord...Help Yourself! in 1956. By the end of the decade he had toured with Stan Kenton and made Slim Gaillard Rides Again! for Dot (1959).

The 1960s found him living in San Diego, where he recorded a few singles, including a rock-and-roll one under the name Slim Delgado, and drifting into acting. He turned up in Mission: Impossible, Marcus Welby, M.D., Medical Center, Then Came Bronson, The Flip Wilson Show and Charlie's Angels, and he played Sam Wesley in the miniseries Roots: The Next Generations (February 1979). He reunited with Slam Stewart at the 1970 Monterey Jazz Festival.

In 1982 Dizzy Gillespie talked him into returning to music. Hep Records captured him in London on October 30, 1982 with Buddy Tate and Jay McShann for Anytime, Anyplace, Anywhere!, and he moved to London in 1983 and worked the European festival circuit, including dates with Arnett Cobb and with George Melly and John Chilton's Feetwarmers. Around Christmas 1985 he recorded the Latin-flavored Siboney at Gateway Studios in Battersea, produced by Joe Massot and not released until 1991. He sang "Selling Out" in the 1986 film Absolute Beginners, appeared on David Sanborn's NBC late-night series Night Music, and was the subject of Anthony Wall's four-part BBC documentary Slim Gaillard's Civilisation in 1989. He passed away in London on February 26, 1991, after a bout with cancer.

Gaillard's trademark was Vout-o-Reenee, a private language of hipster slang and nonsense syllables (he wrote a dictionary of it), delivered in comic vocalese over a swinging rhythm section. His records belong as much to novelty, jive and comedy as to jazz, and a large share of his later public fame came from acting and television work, which is why he sits in the crossover tradition. His appeal resembled that of Cab Calloway and Louis Jordan, but he differed from both in being a genuine improviser whose vocal lines wandered far from the written lyric. AllMusic describes him as a Charlie Christian-style guitarist and a boogie-woogie pianist whose real musical ability was easy to overlook beside the comedy, and the 1945 sessions with Parker and Gillespie show how comfortably he sat alongside bebop. His "Tutti Frutti" (Vocalion 4225, 1938) is the loose basis for the later Little Richard song of the same name.