ick Dastardly and his snickering canine sidekick Muttley first took on the role of villainous duo in the 1968 cartoon series Wacky Races. A year later they became the stars of their own show, titled Dastardly & Muttley in Their Flying Machines.

Although it was never stated outright, the implied setting for the Dastardly & Muttley cartoon took place during World War I, when biplanes ruled the sky. Dastardly formed the head of the Vulture Squadron, a four man team consisting of himself, Muttley, Klunk and Zilly. The team's sole mission was to intercept enemy documents carried by a homing pigeon called Yankee Doodle Pigeon. The squadron's aircraft (which equally took the form of biplanes, monoplanes, and even tri or quad-wing machines) were fitted with extravagant contraptions designed by Klunk. That the contraptions never achieved their desired result was not so much the fault of their inventor, but with the incompetence with which the crew carried out their missions. Time and again the team accidentally destroyed one another's aircraft, many of which lasted no longer than a single scene. By the time the series had reached its 17 episode conclusion, the Vulture Squadron had destroyed a massive number of aircraft without the capture of a single enemy document.

Although Dastardly lead the Vulture Squadron, he took orders from the General, a character that was never fully seen but who constantly checked up on the progress of the group. At the most unlikely of times and locations, a phone would ring and Dastardly would answer, only to be chewed out by the unintelligible shouting of the General, who had every reason to be displeased.

Muttley's primary motivation was the accumulation of war medals. In situations when any extra effort was required, he had a habit of refusing or ignoring an order unless he was promised a medal for his efforts. During the many instances when his comrades were free falling from a destroyed aircraft, Muttley had the unique ability to save them by rotating his tail in the manner of a propeller in order to hover.

Team member Klunk took on the double duty of pilot and inventor of the contraptions that were outfitted to the team's planes. He spoke with a speech impediment that consisted of a lot of clicks, bloops and whistles, accompanied by distorted facial expressions, that made him difficult to understand.

Zilly was a trembling pile of nerves who feared everything. When given orders, he was just as likely to run and hide as carry them out. However, he was the only person who had no difficulty comprehending Klunk, and was frequently asked to interpret what Klunk had said.

Each half-hour episode was made up of two regular stories and two short segments. The first of the short segments was called Wing Dings, which played out one or more jokes in very short skits. The other filler segment was called Magnificent Muttley, a 2-3 minute daydream sequence that followed the adventures of Muttley as he imagined himself in a number of roles (such as king, pirate, movie stuntman, etc.) that had him exacting revenge on Dastardly for constantly giving him orders and taking away his medals.

Post-series, Dastardly and Muttley found further work in the 1985 cartoon Yogi's Treasure Hunt, where they reverted to their original role as the villainous duo of a much larger ensemble cast.