Cabell "Cab" Calloway III was born December 25, 1907, in Rochester, New York, to Cabell Calloway Jr., a Lincoln University graduate, and Martha Eulalia Reed, a Morgan State College graduate who worked as a teacher, church organist, and lawyer. The family moved to Baltimore's Druid Hill neighborhood in 1919, where young Calloway sold newspapers and shined shoes at Pimlico racetrack while developing an early taste for gambling. After he was caught shooting dice on church steps, his mother sent him in 1921 to Downingtown Industrial and Agricultural School in Pennsylvania, a reform institution run by her uncle. He began formal vocal lessons in 1922, graduated from Baltimore's Frederick Douglass High School in 1925, and worked Baltimore nightclubs against his parents' wishes, mentored informally by drummer Chick Webb and pianist Johnny Jones. He later drifted from Chicago's Crane College, choosing nightlife over class, and turned down an offer to play for the Harlem Globetrotters to stay in music.

His break came through his older sister, singer Blanche Calloway, who brought him onto the 1927 tour of the revue Plantation Days; he credited her as the reason he went into show business. In Chicago he sang, drummed, and emceed at "Black and tan" clubs including the Dreamland Café and the Sunset Cafe, where he understudied Adelaide Hall and worked alongside Louis Armstrong, who taught him the rudiments of scat singing. He fronted the Alabamians, moved with them to New York in 1929, and opened at the Savoy Ballroom on September 20, 1929. When that band folded, Armstrong recommended him as his own replacement in the revue Connie's Hot Chocolates, where Calloway made his name singing Fats Waller's "Ain't Misbehavin'."

In 1930, Calloway took over the Missourians, rebranding them Cab Calloway and His Orchestra. The band was booked into Harlem's Cotton Club to cover for Duke Ellington's touring orchestra, proved popular enough to stay on as the house band, and began twice-weekly NBC radio broadcasts that made Calloway one of the first Black entertainers with a nationally syndicated radio presence. On March 3, 1931, at a Brunswick session in New York, he recorded "Minnie the Moocher" (Brunswick 6074), whose nonsense "hi-de-ho" scat refrain became his catchphrase and earned him the nickname "The Hi De Ho Man"; the record is widely credited as the first by a Black artist to sell a million copies. Calloway's rotoscoped dance moves and voice anchored a run of Fleischer Studios cartoons opposite Betty Boop, including Minnie the Moocher (1932) and Snow-White (1933), and he followed the hit that October with the drug-themed sequel "Kickin' the Gong Around" (Brunswick 6209). Through the 1930s he starred in Paramount shorts, played "Reefer Man" in the 1933 feature International House, made his Hollywood feature debut opposite Al Jolson in The Singing Kid (1936), and in 1938 published Cab Calloway's Cat-alogue: A "Hepster's" Dictionary, reportedly the first dictionary published by an African American and later adopted by the New York Public Library as a jive-language reference.

By the late 1930s and into the 1940s, Calloway's orchestra was a proving ground for major jazz talent, carrying at various times Ben Webster, Leon "Chu" Berry, and Illinois Jacquet on saxophones, Milt Hinton on bass, Cozy Cole on drums, Danny Barker on guitar, Doc Cheatham and Dizzy Gillespie in the trumpet section, and Tyree Glenn on trombone. A stripped-down unit from the band, billed as the Cab Jivers, cut "(Hep-Hep!) The Jumpin' Jive" at a New York session on July 17, 1939 (Vocalion 5005), a million-selling side later revived by the Blues Brothers and by Joe Jackson. A backstage spitball incident in 1941 ended with Calloway firing Gillespie and Gillespie stabbing him in the leg, effectively closing that chapter of the collaboration. During World War II, Calloway toured to entertain troops and recorded topical specialty numbers, and in 1943 he appeared in Stormy Weather, one of the first Hollywood films built around a Black cast, alongside Lena Horne, Bill "Bojangles" Robinson, and Fats Waller. Poor financial decisions and heavy gambling losses caught up with him by decade's end, and his full orchestra broke up around 1948, a casualty of the same economics that ended most of the big bands.

Through the 1950s and 1960s Calloway rebuilt his career around theater and cabaret work. He played Sportin' Life in the Blevins Davis/Robert Breen touring revival of Porgy and Bess from 1952 to 1954, a run that included a State Department-sponsored European tour and a broadcast performance from Berlin. He led The Cotton Club Revue of 1958 on Broadway and on record for Gone Records, with the show later touring South America, and in 1961 and 1962 he provided halftime entertainment on the road with the Harlem Globetrotters. He took a rare dramatic film role in The Cincinnati Kid (1965) with Steve McQueen, and in 1967 he co-starred with Pearl Bailey, alongside his own daughter Chris Calloway, in the all-Black Broadway cast of Hello, Dolly!, whose RCA Victor cast recording (LOC/LSO-1147) is still regarded by many theater critics as the finest version of the score on record.

Calloway's final decades brought a second wave of fame. His 1976 autobiography, Of Minnie the Moocher and Me, reprinted the Hepster's Dictionary as an appendix, and a 1978 disco remake of "Minnie the Moocher" charted on Billboard's R&B listings. His 1980 cameo in The Blues Brothers, reprising "Minnie the Moocher" in white tie and tails, introduced him to an entirely new audience; director John Landis later summed up his influence bluntly: "Cab Calloway is hip-hop." He kept performing into his eighties, taping a BBC special from London's Ritz Hotel in 1985 with Doc Cheatham and Max Roach, recording "Minnie the Moocher" again with the Cincinnati Pops in 1988, appearing with the Baltimore Symphony and in Janet Jackson's "Alright" video in 1990, and touring European jazz festivals as late as 1992. A fall at home forced him to withdraw from a scheduled 1993 concert; he suffered a stroke on June 12, 1994, and died of pneumonia on November 18, 1994, at a nursing home in Hockessin, Delaware, at age 86. He was buried at Ferncliff Cemetery in Hartsdale, New York.

Calloway built his career less as an instrumentalist than as a bandleading showman: a scat vocalist who absorbed the technique directly from Louis Armstrong, a physical performer whose zoot suit and "hi-de-ho" call-and-response routines turned Cotton Club broadcasts into mass entertainment, and a shrewd bandleader who stocked his orchestra with some of the era's best soloists. His gliding backstep, called "the Buzz" in his own day, has repeatedly been cited as a forerunner of Michael Jackson's moonwalk, and critics and directors alike have traced a direct line from his hi-de-ho showmanship and rhythmic vocal patter to James Brown, Michael Jackson, and hip-hop performance generally. He charted on Billboard across five separate decades, an unusually long commercial run for a swing-era bandleader. His reach extended well beyond his own generation: pianist and composer Pepper Adams grew up in Depression-era Rochester and Detroit absorbing Fats Waller, Fletcher Henderson, Jimmie Lunceford, Duke Ellington, and Calloway from records, one strand of the big-band tradition that fed directly into Adams's own bebop and hard-bop vocabulary a generation later (Pepper Adams profile).