Van Dyke's first major role was on stage in Bye Bye, Birdie in 1960, for which he won a Tony Award. He then starred in his own sitcom, The Dick Van Dyke Show, which ran for five seasons -- in the lead role of Rob Petrie, Van Dyke won three Emmy Awards. He slowly transitioned out of television into movie acting in Bye Bye, Birdie (1963), What a Way to Go (1964) and, most notably, Walt Disney's Mary Poppins (1964), in which he played Bert, a Cockney chimney sweep, and also played, in heavy disguise, the elderly owner of the bank. Van Dyke's attempt at a Cockney accent was widely ridiculed (especially in the UK), but the film also showed his versatility as a singer and dancer.

After the mid-1960s, Van Dyke was in a number of relatively unsuccessful movies (though one, a children's film called Chitty Chitty Bang Bang, is still well-known, especially with the recent stage musical). His career seemed essentially over by 1990 when Van Dyke, whose usual role had been the amiable hero, took a villainous turn in Dick Tracy. He received positive reviews that led him to star in a series of TV movies on CBS that became the foundation for his popular television drama, Diagnosis: Murder, which ran from 1993 to 2001.

Dick Van Dyke is the brother of actor Jerry Van Dyke. Dick's son Barry Van Dyke and grandson Carry Van Dyke are also actors: both Barry and Carry acted with Dick on Diagnosis: Murder.