Charles Daly Barnet was born on October 26, 1913, in New York City, the son of Charline Daly and Willard Barnet. His parents divorced when he was two, and he was raised by his mother and her grandparents; his maternal grandfather, Charles Frederick Daly, was a vice-president of the New York Central Railroad as well as a banker and businessman, and the family wealth later let Barnet treat music as a career he could leave whenever he liked. He attended boarding schools in the New York and Chicago areas, learned piano and saxophone as a child, often skipped class to hear bands and look for work, and chose music over the law career his family wanted for him. By sixteen he had toured with a satellite band of Jean Goldkette's and was playing tenor saxophone in Frank Winegar's Pennsylvania Boys in New York. In 1931 he moved to Hollywood, where he worked as a film extra and tried to interest local bandleaders in hot music, then unpopular in the Depression, and late in 1932, at eighteen, he returned east and persuaded a contact at the CBS artist bureau to let him lead an orchestra.

Barnet began recording as a leader in October 1933 during an engagement at New York's Park Central Hotel, but he was not a great success for most of the decade, regularly breaking up his band and changing its style. In early 1935 he tried to introduce swing at the Hotel Roosevelt in New Orleans, where, according to the usual account, Louisiana governor Huey Long disliked the new sound and had the band run out of town by luring its members to a bordello that was then raided. He arranged for Joe Haymes to take over several of his out-of-work sidemen and spent a spell in Havana, and in 1936 he led another swinging edition that featured the vocal quartet the Modernaires before it too faded. That same year, when he was in the audience at the original Famous Door on 52nd Street, the club fired Billie Holiday and Teddy Wilson for mingling with him. His first stable band came together between 1939 and 1941, opening with a hit version of Ray Noble's "Cherokee," arranged by the trumpeter Billy May, and a successful run at the Famous Door. May, who had come to New York at twenty-two as chief arranger, wrote roughly seventy arrangements for the band that Bluebird issued before Glenn Miller hired him away in 1940, among them the Barnet-and-May burlesque "The Wrong Idea," which mocked the "sweet" bands of the day.

Barnet was one of the first white bandleaders to run an integrated orchestra, and AllMusic dates his mixed bands to as early as 1935. The trumpeter Roy Eldridge spent time in his ranks, and Lena Horne toured with the band in 1940 and 1941 and recorded "Good-for-Nothin' Joe" and "You're My Thrill" with it for Victor in January 1941. The orchestra was booked into Harlem's Apollo Theater, unusual for a mostly white group, and set an attendance record there. Barnet was an outspoken admirer of Duke Ellington and of Count Basie, and Ellington recorded Barnet's "In a Mizz." When a fire at the Palomar Ballroom in Los Angeles on October 2, 1939, destroyed the band's instruments and arrangements and ended Barnet's last show there, Basie, who was booked into the room two days later, lent him some of his charts. In 1942 he hired the bassist Oscar Pettiford to play bass duets alongside his own bassist, Chubby Jackson, and the seventeen-year-old pianist Dodo Marmarosa was in the band from October 1943 to March 1944, making his recording debut with it on "The Moose."

Barnet recorded for Decca from 1942 to 1946, and "Skyliner," a Barnet original arranged by Neal Hefti, became a best-seller in 1944. The singer Kay Starr was with the band from 1943 to 1945, and the clarinetist Buddy DeFranco and the guitarist Barney Kessel also passed through. In 1947 Barnet began shifting from swing to bebop: Clark Terry was his star trumpeter that year, and in 1949 his trumpet section included Maynard Ferguson, Doc Severinsen, Rolf Ericson, and Ray Wetzel. Barnet lost interest and broke up the band near the end of 1949. He took up semi-retirement, which his family fortune made possible, and returned only for short tours and occasional recording dates. Billy May arranged another 36 titles for him between 1954 and 1970, a 1956 album, Dance Bash, was assembled from sessions made between 1947 and 1952, and in 1958 he remade "Cherokee" in stereo for Everest. In September 1964 he arranged a private party at the San Jacinto country club in Palm Springs so that Ellington's orchestra could play for an audience of friends; Barnet did not play.

Barnet was married eleven times, the last time to Betty Thompson for 33 years, and had one son, Charles D. Barnet Jr. He lived in Palm Springs and San Diego and kept a 46-foot boat in San Diego. His autobiography, Those Swinging Years, written with Stanley Dance, was published in 1984. He passed away on September 4, 1991, at Hillside Hospital in San Diego, at 77, from complications of Alzheimer's disease and pneumonia.

Barnet was chiefly a tenor saxophonist, and AllMusic hears an original sound grown out of the Coleman Hawkins school. In the late 1930s he added alto saxophone, on which he could imitate Johnny Hodges, and then soprano, an instrument that had gone out of fashion after the 1920s and that only Sidney Bechet and Barnet played regularly in the swing era. As a leader he leaned toward the sound of Duke Ellington's band, which his own orchestra could imitate closely at its peak in 1939 to 1942, and toward the riffing drive of Count Basie's, and he set himself against what he called syrupy arrangements. His records ranged from hard-swinging instrumentals to novelty numbers, and by 1947 the band was playing bebop-tinged charts. AllMusic judges his jazz importance to be concentrated in a single decade, 1939 to 1949, and credits him with leading integrated bands years before most of his white contemporaries. His bands had a reputation for rowdiness; in his autobiography he contrasted his easygoing approach with the strict dress and conduct of Glenn Miller's band. James Moody named Barnet among his earliest influences, according to Moody's own profile.