Dave Bartholomew was born Davis Bartholomew on December 24, 1918, in Edgard, Louisiana, to Mary and Louis Bartholomew. He first learned his father's instrument, the tuba, and then took up the trumpet under Peter Davis, a teacher who had also taught Louis Armstrong. Around 1933 the family moved to New Orleans, where he played in local jazz and brass bands, among them Papa Celestin's band and Fats Pichon's band on a Mississippi riverboat. He took over Pichon's band in 1941, spent a period in Jimmie Lunceford's orchestra, and then joined the US Army, where he learned scoring and arranging as a member of the 196th Army Ground Forces Band.

Back in New Orleans after the war, he was leading his own dance band by November 1945, Dave Bartholomew and the Dew Droppers, named for the Dew Drop Inn hotel and nightclub. The group became the house band of the city's rhythm and blues, and the historian Robert Palmer later called it a model for early rock and roll bands around the world. Its players included the saxophonists Alvin "Red" Tyler, Herb Hardesty and Clarence Hall, bassist Frank Fields, guitarist Ernest McLean, pianist Salvador Doucette and drummer Earl Palmer, with saxophonist Lee Allen arriving later. In 1947 the club owner Don Robey brought the band to Houston, where Bartholomew met Lew Chudd, the founder of Imperial Records. That September the band made its first records, including "She's Got Great Big Eyes," at Cosimo Matassa's studio for De Luxe, and its first hit, "Country Boy," reached No. 14 on Billboard's R&B chart in early 1950.

Chudd made him Imperial's New Orleans A&R man in 1949, and in December of that year Bartholomew produced "The Fat Man," a young pianist named Fats Domino's first record, with his own band behind him. It reached No. 2 on the R&B chart and sold more than a million copies. After a disagreement with Chudd he left Imperial at the end of 1950 and recorded for Decca, King and Specialty, writing and recording "My Ding-a-Ling" for King in January 1952 (Chuck Berry's rewritten version went to No. 1 in 1972) and producing Lloyd Price's "Lawdy Miss Clawdy" for Specialty, an R&B No. 1 that summer. Back at Imperial he co-wrote and produced the run of Domino hits that began crossing to the pop chart with "Ain't That a Shame" in 1955, followed by "I'm in Love Again" and "Blue Monday" in 1956, "I'm Walkin'" in 1957, "I'm Gonna Be a Wheel Someday" in 1959 and "Let the Four Winds Blow" in 1961. He also wrote, arranged and produced for Smiley Lewis ("I Hear You Knocking," "One Night"), the Spiders, Chris Kenner, Earl King, Tommy Ridgley, Robert Parker, T-Bone Walker, Roy Brown and Frankie Ford, produced Shirley and Lee's "Let the Good Times Roll" for Aladdin, and, according to the profile of James Booker, produced the teenage pianist's 1954 debut single. His wife Pearl King, whom he married in 1942, shares writing credit on several of the songs.

Under his own name he made two LPs for Imperial, Fats Domino Presents Dave Bartholomew and His Great Big Band (1961), built on Domino's hits, and New Orleans House Party (1963). After Imperial was sold to Liberty in 1963 he stayed in New Orleans, worked for Trumpet and Mercury, and in 1967 started his own Broadmoor label, which folded the next year when its distributor, Dover, collapsed. In the 1970s and 1980s he led a traditional Dixieland band in New Orleans and took part in Domino's international tours. Dave Bartholomew's New Orleans Jazz Band (Broadmoor, 1981) has him on trumpet with the clarinetist Willie Humphrey and the trombonist Waldren "Frog" Joseph, playing Dixieland standards alongside his own Domino-era hits. He was inducted into the Rock and Roll Hall of Fame in 1991 as a non-performer, and is also a member of the Songwriters Hall of Fame and the Louisiana Music Hall of Fame. In the 1990s he recorded two Dixieland CDs with the Maryland Jazz Band of Cologne, Walking to New Orleans and New Orleans 'Yea Yea' Breakdown (both 1995), and a large-band set with New Orleans horn players, New Orleans Big Beat (1998).

He celebrated his 100th birthday on Christmas Eve 2018, though plans for a concert in his honor were set aside when he was hospitalized. Bartholomew passed away of heart failure at East Jefferson General Hospital in Metairie, Louisiana, on June 23, 2019, at the age of 100. After the death of Pearl in 1967 he had married Rhea Douse, with whom he had four sons and a daughter.

Bartholomew is a crossover figure in the plainest sense: his fame rests on New Orleans rhythm and blues and early rock and roll rather than on jazz records, and, as the Rock and Roll Hall of Fame's essay on him notes, he never made the pop charts under his own name. What he brought to that music was a jazz musician's training. He came up in New Orleans brass and jazz bands, passed through Jimmie Lunceford's orchestra and learned arranging in an Army band, and he turned that into tight horn-section arrangements over a steady, danceable beat, with saxophonists such as Herb Hardesty and Lee Allen and the drummer Earl Palmer in the band. AllMusic calls him the self-proclaimed inventor of the "Big Beat," and the Rock Hall cites him as a key figure in the move from jump blues and swing to R&B. Cosimo Matassa, who engineered the sessions, remembered how firmly he insisted on discipline from the players. His trumpet and bandleading return openly to jazz in the 1961 big-band LP, the 1981 and 1995 Dixieland sets and his late appearances at festivals, which makes him a bridge between the older New Orleans jazz tradition and the rock and roll that grew out of the city's dance bands. Many of his songs were recorded by others, from Pat Boone and Gale Storm to Elvis Presley, Ricky Nelson and Dave Edmunds.