Messick first wanted to be a ventriloquist, and even for a time supported himself as one. His big break came in the mid-1940s. At MGM, Tex Avery was doing the Droopy Dog cartoons. The regular voice actor, radio actor Bill Thompson, was not available. Daws Butler, who voiced characters for MGM, suggested that Avery seek out Messick. And so, Messick was called on to voice Droopy. Later, in the mid-1950s, when Bill Thompson parted ways with MGM, Messick took over the role of Droopy.

Messick and Butler became a voice acting team for the Hanna-Barbera unit in 1957 with the arrival of Ruff and Reddy. Don was Ruff the cat and the Droopy-sounding Professor Gizmo. Butler was the southern-speaking dog, Reddy. Messick also narrated the show, which played out like an animated soap opera.

From 1957 to 1965, Butler and Messick gave voice to a staggering number of characters. Always the side-kick, Messick’s characters weren’t headliners. His notable roles in this era were Boo Boo Bear, Ranger Smith, Major Minor, Pixie Mouse, and Astro.

Messick was used primarily for his narration skills, which were heard on all of those cartoons in which Daws Butler starred. The off-camera voice telling us about the latest fiasco Quick Draw McGraw got himself into was Don Messick. Butler was Quick Draw and his Mexican side-kick, Baba Looey. Messick would eventually star in a cartoon series: Ricochet Rabbit. This character was paired with the slow-poke Deputy Droop-a-Long (Mel Blanc voiced the deputy).

The outer space cartoons were where Messick really shone. His unique gift at creating noises and sounds for weird space creatures and aliens really helped the space cartoons in a big way. His “Ranger Smith” voice was often heard as space villains. His narrator voice was given to Vapor Man, Dr. Benton Quest, and Multi Man. His narrating voice was also heard on Hong Kong Phooey (1974) and Laff-A-Lympics (1977).

In 1969, he was cast as the cowardly canine Scooby-Doo on Scooby-Doo, Where Are You!. This role would remain Messick’s biggest and best-known. He voiced the Great Dane through all of the various versions of Scooby-Doo: on TV in numerous formats from 1969 to 1985, four telefilms, and a number of commercials as well. Messick was still voicing the role when A Pup Named Scooby-Doo came along from 1988 to 1991.

In the 1980s his biggest role was Papa Smurf on the Smurfs series from 1981 to 1990. He also voiced Ratchet (the Autobot doctor), Gears, and Constructicon Scavenger on The Transformers.

In the mid-1980s, new episodes of The Jetsons were produced. Messick was back as Astro, RUDI, and new voice Uniblab, a pesky robot that worked for Mr. Spacely (voice of Mel Blanc).

In the 1990s, he voiced Hamton J. Pig in FOX’s Tiny Toon Adventures and its spin-offs from 1991 to 1995. FOX also had Messick return to his Droopy character for Droopy: Master Detective in 1993.

In 1996, at the age of 70, Messick suffered a stroke while inside a cartoon studio recording voices. It has been said that Messick turned pale, looked over at the director and said, “I can’t do this anymore”, then stumbled out to his car and drove home. A week later, Messick’s agent sent word that he had retired.

On October 24, 1997, at age 71, Messick suffered a second stroke and died of complications shortly afterward.