He appeared in a number of British films and television series, as aristocrats, including starring roles in the television comedy series The World of Wooster (as "Bingo Little"), and in the comedy film One of Our Dinosaurs Is Missing (as "Lord Southmere"), as well as appearing in the James Bond spoof film Casino Royale.

Nimmo made his name as the Reverend Mervyn Noote in the British sitcom All Gas and Gaiters (1966). At the time it was considered rather controversial because the main characters were senior churchmen  By the time the series finished, Nimmo was identified with the stereotype of a traditional British clergyman and he went on to play a bungling monk in another BBC clerical sitcom, Oh, Brother!, and a Roman Catholic priest in its sequel series, Oh, Father! In 1969, Nimmo received an award for his performances in both sitcoms, when the Royal Television Society awarded him a silver medal.Another sitcom in which he appeared in a starring role as a clergyman, many years later, was Hell's Bells (by now promoted to a dean) which ran for one series in 1986. He also appeared as the Reverend Jonathan Green in a television production of Cluedo. He became so well known for his clerical parody that, in the 1975 The Goodies episode "Wacky Wales", a "team of Derek Nimmos" played in a spoof "Ecclesiastical Rugby Sevens" competition.

In 1966, he appeared in the second series of The Bed-Sit Girl. Nimmo appeared on stage in many West End plays and starred in the musical Charlie Girl, which contained a scene specially written to allow him to perform his party trick of wiggling his toes. He also became a regular panellist on the popular BBC radio show Just a Minute,and had a chat show on BBC Television, If It's Saturday, It Must Be Nimmo, from 24 October to 19 December 1970, though it was felt that he seemed less at ease as a chat show host. Having been away from television for some time, he made an appearance in the Australian television series Neighbours in 1990, playing Lord Ledgerwood alongside Madge and Harold Bishop.