Thomas Francis Dorsey Jr. was born on November 19, 1905, in Mahanoy Plane, Pennsylvania, the second of four children of Thomas Francis Dorsey Sr., a bandleader, and Theresa (Langton) Dorsey. He and his older brother Jimmy, who was born less than two years before him, came up together and became known as the Dorsey Brothers. Tommy studied trumpet with his father before switching to trombone, and in his early years he was known on both horns; he recorded hot trumpet solos in the late 1920s, among them "The Spell of the Blues" with the Dorsey Brothers Orchestra for OKeh on January 26, 1929. At 15, on Jimmy's recommendation, he replaced Russ Morgan in the Scranton Sirens, a territory band. The brothers then worked in bands led by Tal Henry, Rudy Vallee, Vincent Lopez, and Nathaniel Shilkret. In 1923 Tommy followed Jimmy to Detroit to join Jean Goldkette's band, in 1925 he returned to New York to play with the California Ramblers, and in 1927 he joined Paul Whiteman. By 1930 he was one of New York's most successful freelance radio and recording trombonists, heard on sessions with Bix Beiderbecke's Rhythm Jugglers, Joe Venuti and Eddie Lang, and Red Nichols, and on the March 1928 all-star Victor session under Shilkret that also included Benny Goodman, Glenn Miller, and Venuti.

The brothers began recording as the Dorsey Brothers for OKeh in 1928 and had their first hit with "Coquette" in 1929. In 1934 the Dorsey Brothers Orchestra signed with Decca and became a touring band with Tommy as front man, built on an unusual lineup of one trumpet, three trombones, three saxophones, and four rhythm. Miller was a member in 1934 and 1935 and wrote four tunes for it, and in 1935 the orchestra had two number-one records, "Lullaby of Broadway" and "Chasing Shadows." The brothers' quarrels reached a breaking point in May 1935 over the tempo of "I'll Never Say Never Again Again": Tommy walked off the bandstand during an engagement at the Glen Island Casino and left for good. He took over Joe Haymes's band, signed it to RCA Victor, and turned it into Tommy Dorsey and His Orchestra. "On Treasure Island" was the first of four hits for the new band in 1935, and the theme he adopted, "I'm Getting Sentimental Over You," had been recorded by the Dorsey Brothers in 1932 and 1934 before Tommy recorded it for Victor in September and October 1935. Jimmy kept the Dorsey Brothers Orchestra.

The new band was known mainly for ballads at dance tempos and for vocal numbers, and after the 1935 sessions Dorsey's manager steered him away from the hot jazz he had mixed with his lyrical playing. He kept a small Dixieland group drawn from the band, the Clambake Seven, to play during performances, and he became co-host and then host of radio's Raleigh-Kool Program. Jazz players still passed through: Bud Freeman sat in the saxophone section from 1936 to 1938, and the trumpeter Bunny Berigan worked as a jazz soloist on Dorsey's radio program and records in late 1936 and early 1937, where his solo on the hit "Marie" became a signature performance. On March 31, 1937, Dorsey joined Berigan, Fats Waller, guitarist Dick McDonough, and drummer George Wettling for A Jam Session at Victor, an improvised date built on "Honeysuckle Rose" and a blues that reached number four on the pop charts. In 1938 he recorded a big-band arrangement of Pine Top Smith's "Boogie Woogie," which became a hit in 1943 and 1945 and the best-selling record of his career. By 1939 he knew the band was criticized for lacking jazz feeling, and in response he hired the arranger Sy Oliver away from Jimmie Lunceford. Oliver, who became one of the first Black musicians with a prominent role in a white band, wrote up-tempo charts including "On the Sunny Side of the Street" and "T.D.'s Boogie Woogie," and composed two of the band's signature instrumentals, "Well, Git It!" and "Opus One." His arrival helped draw jazz players such as the drummer Buddy Rich, who joined in 1939.

In November 1939 Dorsey hired Frank Sinatra away from Harry James. Sinatra's first appearance with the band came on January 26, 1940, in Rockford, Illinois, and he made about eighty recordings with it through 1942. "I'll Never Smile Again," with Sinatra and the Pied Pipers, topped Billboard's first national best-selling retail records chart on July 27, 1940, and stayed at number one for twelve weeks; Dorsey takes the trombone solo in the break and again near the end. The Pipers' lead singer Jo Stafford had joined the band in 1939 and Connie Haines followed in 1940, while the arrangers Axel Stordahl and Paul Weston, both with the band from 1936, shared the book with Oliver, who took the up-tempo numbers while Stordahl wrote the ballads. Sinatra later said he learned breath control by watching Dorsey play. A contract dispute was settled in August 1942, and Dorsey said goodbye to Sinatra on September 3. The band's later years brought in the trombonist Nelson Riddle (1944 to 1945), the arranger Bill Finegan (1942 to 1950), the trumpeter Charlie Shavers (from 1945, off and on until Dorsey's death), and, after his 1943 marijuana arrest, the drummer Gene Krupa; Rich returned in 1945. When Artie Shaw broke up his band in 1942, Dorsey hired Shaw's string section. He also lent Miller money in 1938 to start his own band, owned two music publishing companies and, from about 1944, a Los Angeles ballroom, the Casino Gardens, and appeared in films including Ship Ahoy (1942), Girl Crazy (1943), and Du Barry Was a Lady (1943).

Dorsey disbanded the orchestra at the end of 1946, but the RCA Victor album All Time Hits reached the top ten in February 1947 and "How Are Things in Glocca Morra?" followed in March, and he reorganized a big band in early 1947. The biographical film The Fabulous Dorseys (1947) had the brothers playing themselves. Tommy returned to Decca in the early 1950s, and after Jimmy gave up his own band the two led a combined Dorsey Brothers Orchestra, with Tommy as leader and Jimmy as co-leader and featured soloist. The brothers appeared on Jackie Gleason's CBS show on December 26, 1953, and then hosted the CBS series Stage Show from 1954 to 1956, on which Elvis Presley made his first national television appearances in January 1956. Tommy passed away on November 26, 1956, at his home in Greenwich, Connecticut, a week after his 51st birthday; he had been taking sleeping pills and choked in his sleep after a large meal. Jimmy led the band until his own death the next year, and the Tommy Dorsey Orchestra has continued under other leaders, among them Warren Covington, Sam Donahue, and the trombonist Buddy Morrow, who led it from 1977 until his death in 2010. In 1982 "I'll Never Smile Again" became the first of three Dorsey recordings in the Grammy Hall of Fame; "I'm Getting Sentimental Over You" and "Marie" followed in 1998, and the U.S. Postal Service issued a stamp honoring Tommy and Jimmy in 1996.

Dorsey was a trombonist of unusual technical control, with a smooth, singing tone and long legato phrasing that earned him the nickname "Sentimental Gentleman of Swing," and he said his trombone style was heavily influenced by Jack Teagarden. His best-known playing is on ballads, where his breath control and sustained line were models for other players and, as Frank Sinatra said, for singers; he was also a precise, demanding leader who, in the recollection of the clarinetist Buddy DeFranco, wanted every part played exactly. The jazz case for him rests on several things: the hot solos he recorded in the 1920s, the Clambake Seven's Dixieland sets, the Jam Session at Victor date, the swing arrangements of Sy Oliver, and a band that over the years carried the soloists Bunny Berigan, Bud Freeman, Ziggy Elman, Charlie Shavers, Buddy DeFranco, and Buddy Rich. Against that stands the commercial core of his output: seventeen number-one records and more than 280 chart entries, most of them dance-band ballads and vocal features, which is why his reputation sits between hot jazz and sweet-band pop. His own band took the criticism seriously enough in 1939 to hire Oliver, and the records from the early 1940s, "Well, Git It!" and "Opus One" among them, are the ones most often cited for the band's swing. He is also remembered as a talent finder: Sinatra, Rich, and Nelson Riddle all passed through his orchestra before their larger careers, and Stordahl, Weston, and Oliver were arrangers he kept on staff.