The series is a spin-off of Wacky Races and its title references the 1965 film and song 'Those Magnificent Men in Their Flying Machines'.

The show's original working title was 'Stop That Pigeon,' a phrase also repeated in the theme song.

The entire show featured only two voice actors: Paul Winchell, who voiced Dick Dastardly, the General, and occasional guest characters, and Don Messick, who voiced Muttley, Klunk, Zilly, the Narrator, and nearly all other guest characters.

Each 22-minute episode was broadcast over a 30-minute network slot and included two Dastardly & Muttley stories, one Magnificent Muttley segment, and two or three short Wing Dings gags.

Dastardly's car from Wacky Races made cameo appearances in a few Magnificent Muttley shorts, including 'The Marvelous Muttdini' and 'Admiral Bird Dog'.

Psychobilly band the Reverend Horton Heat covered the show's theme song in 1995 as a medley with the Jonny Quest theme on the compilation album Saturday Morning: Cartoons' Greatest Hits.

Hip-hop group Madvillain references the show's characters in their song 'Accordion' from the album Madvillainy.

In the 2007 BBC Robin Hood episode 'Lardner's Ring,' the Sheriff of Nottingham yells 'We must catch the pigeon! Catch the pigeon NOW!' in a manner mimicking Dick Dastardly.

Due to licensing issues, Hanna-Barbera created renamed versions of the characters, Mumbly and Dread Baron, who closely resemble Muttley and Dick Dastardly, for the 1978 series Laff-A-Lympics; Dread Baron was later revealed in the comic books to be Dastardly's brother.