Humphrey Richard Adeane Lyttelton, known to everyone as Humph, was born on May 23, 1921, at Eton College, where his father, George William Lyttelton, was a house master. His father was the second son of the 8th Viscount Cobham, which placed the family within the Lyttelton clan of cricketers and politicians; the politician and sportsman Alfred Lyttelton was his great-uncle. He went from Sunningdale Preparatory School to Eton, where he fell for the records of Louis Armstrong and the English trumpeter Nat Gonella, taught himself the trumpet, and in 1936 formed a school quartet. After Eton he spent a spell at the Port Talbot steel plate works in South Wales, was called up, and was commissioned in the Grenadier Guards on November 29, 1941. He saw action at Salerno during Operation Avalanche, coming ashore with a pistol in one hand and his trumpet in the other. On VE Day in 1945 he played the trumpet from a wheelbarrow in the street celebrations, an impromptu first broadcast performance whose BBC recording survives.

Demobilised, he studied for two years at Camberwell Art College and met the clarinetist and cartoonist Wally Fawkes, who signed his drawings "Trog." In 1947 both joined George Webb's Dixielanders, a semi-professional band widely counted as the first British revivalist jazz group. Lyttelton left the Dixielanders in January 1948 to form his own band, and Fawkes went with him; Webb himself joined the new band that September and stayed until June 1951, and the brothers Keith Christie (trombone) and Ian Christie (clarinet) soon completed a front line that became a leader of the postwar New Orleans revival. He signed with Parlophone in late 1949, and the label went on issuing his records through the 1950s. In 1949 he also began working beside Fawkes on the Daily Mail strip Flook, staying with the paper until 1956. That same year he recorded with Sidney Bechet, which meant defying the Musicians' Union's restrictions on working with visiting American players.

By the early 1950s he was steering away from strict revivalism toward the mainstream swing of players such as the trumpeter Buck Clayton. He added saxophones to the band in 1953, and when the alto saxophonist Bruce Turner made his debut at Birmingham Town Hall that year, a banner in the audience read "Go Home Dirty Bopper!" On April 20, 1956, in London, the band recorded his fast instrumental blues "Bad Penny Blues." Johnny Parker's boogie-woogie piano riff was pushed to the front by Joe Meek, the engineer for producer Denis Preston, and the record became the first British jazz record to reach the UK Top 20, staying there for six weeks; Paul McCartney later modeled the piano part of "Lady Madonna" on its riff. From 1958 he settled on an eight-piece band with alto, tenor and baritone saxophones, which served as a training ground for players including Tony Coe, Joe Temperley, Kathy Stobart, Jimmy Hastings, Alan Barnes and Karen Sharp.

Lyttelton's band backed visiting Americans throughout those years. Jimmy Rushing toured Britain with it in 1957 and 1958, and a live set from Lyttelton's club at 100 Oxford Street on September 11, 1957, was recorded by Meek. Clayton recorded with the band in the early 1960s and toured with it repeatedly, regarding Lyttelton as a brother; Clayton, Vic Dickenson and Big Joe Turner toured together in 1965, and in later decades Lyttelton made records with Buddy Tate, Kenny Davern and Bud Freeman. He was the subject of the television programme This Is Your Life in 1958. In 1983 he founded Calligraph Records, which reissued his Parlophone-era recordings and released the band's later work. He co-led two Calligraph CDs with Acker Bilk, At Sundown (1992) and Three in the Morning (1994), and the band joined the Giants of British Jazz tours with Bilk and George Melly. A demo by the American singer Stacey Kent was played on his Radio 2 programme, and he introduced her to British audiences; he made Between Friends in 2000 with Kent and the saxophonist Jim Tomlinson. In 2001 his band played on "Life in a Glasshouse," the closing track of Radiohead's Amnesiac; in 2003 he issued Trouble in Mind with the singer Elkie Brooks, with whom he had first worked in the early 1960s.

Lyttelton was equally prominent off the bandstand. From 1967 until April 2007 he presented The Best of Jazz on BBC Radio 2, and from 1972 he chaired the BBC Radio 4 comedy panel game I'm Sorry I Haven't a Clue, where his deadpan manner made him the oldest active panel-show host in Britain by the time of his death. He published a shelf of books, among them the memoir I Play as I Please (1954), and was a calligrapher who served as president of the Society for Italic Handwriting. He turned down a knighthood in 1994.

On April 18, 2008, the producers of I'm Sorry I Haven't a Clue announced that he was going into hospital to repair an aortic aneurysm; he postponed the operation and performed on all but the last night of the spring tour, then passed away on April 25, 2008, following the surgery. A humanist funeral was held on May 6, 2008. BBC Radio 2 listeners voted him Jazz Artist of the Year on July 23, 2008, and a celebration concert took place at the Hammersmith Apollo on April 25, 2010, organized by his son Stephen, who founded the Humph Trust to support young jazz musicians.

Lyttelton began as a devotee of Louis Armstrong and the New Orleans revival, and his first Parlophone recordings keep to that repertoire of stomps, rags and blues. He did not stay there. From the early 1950s he moved toward the saxophone-augmented mainstream approach favored by American players such as Buck Clayton, a change some of his original fans resented, and his repertoire grew to take in lesser-known pieces by Duke Ellington and even "The Champ" from Dizzy Gillespie's band book; his 1975 album Take It from the Top is subtitled a dedication to Ellington. His own trumpet playing was declamatory and blues-soaked, a tone that drew praise from Armstrong himself. He saw himself primarily as a bandleader, and the band became a training ground for a long line of British saxophonists and trombonists. Alongside the music he worked as a cartoonist, author and calligrapher, and for generations of listeners his voice on radio was as familiar as his trumpet, but the jazz band remained the center of his working life and toured until his final spring.