He has also voiced Baby Kermit in the original Muppet Babies, Oswald the Lucky Rabbit in Epic Mickey and its sequel; Megatron, Galvatron, Soundwave and various characters in the Transformers franchise; Santa's Little Helper and Snowball II on The Simpsons; Shao Kahn and Reptile in the 1995's Mortal Kombat film adaptation; the titular protagonist of the Curious George franchise; Garfield on The Garfield Show; Nibbler on Futurama; the titular character of Jabberjaw; Speed Buggy for the Scooby-Doo franchise; Astro and Orbitty on the 1980s revival of The Jetsons; and various characters in The Smurfs.

[6] His next major character voice was for Wonder Dog (which was inspired by Scooby-Doo) and Marvin White on the 1973 series Super Friends (also produced by Hanna-Barbera).

He provided the voices for Mr. Plotz, Runt, Ralph the Guard, Buttons, and other characters on Animaniacs, Gogo Dodo, Furball, Beeper, and others on Tiny Toon Adventures, Hector the Bulldog on The Sylvester & Tweety Mysteries, and Tom Cat, Jerry Mouse, and McWolf, the main antagonist to Droopy and his nephew Dripple on Tom & Jerry Kids Show and Droopy, Master Detective.

He also voiced Gus Goose, Salty the Seal, Figaro, Pegasus from Hercules, Abu the Monkey from Aladdin, "Aracuan Bird" & Cri-Kee from Mulan in the House of Mouse from 2001 to 2003.

Welker has also created the vocal effects for many animals and creatures in films, including Abu the monkey, Rajah the tiger, and the Cave of Wonders in Aladdin (1992), its two sequels, the television series, and the remake (2019), Arnold the Pig in the television film Return to Green Acres (1990), the whales in Free Willy 2: The Adventure Home, Shao Kahn and Reptile in the Mortal Kombat movie (1995), the Martians in Tim Burton's Mars Attacks!

He performed Spock's screams in Star Trek III: The Search for Spock (1984) and voiced The Thing in The Golden Child (1986), Jinx the robot in SpaceCamp (1986), Totoro in the 2005 English version of Studio Ghibli's film My Neighbor Totoro (1988), Alien Sil in Species (1995), Malebolgia in Spawn (1997), and Gargamel's cat Azrael in Sony Pictures Animation's live action/animated film versions of The Smurfs.

[10] On-camera television appearances included roles on Laugh-In, Love, American Style, The Partridge Family, and The Don Knotts Show.

He played a prosecutor in the highly acclaimed ABC special The Trial of General Yamashita and as Captain Pace beside Richard Dreyfuss' Yossarian in Paramount Television's pilot Catch-22.

He voiced several Decepticons, including the leader Megatron, Soundwave, Skywarp, Mixmaster, Rumble, Frenzy, Ravage, and Ratbat, as well as Autobots Mirage, Trailbreaker, and Sludge.

In the 2015 follow-up series Transformers: Robots in Disguise, Welker once again reprised his role as Soundwave, who has broken his vow of silence since the events of Prime.

Welker returned to two of his Transformers roles when he portrayed Megatron and Soundwave as part of a spoof in a third-season episode of Robot Chicken, which aired shortly after the release of the first installment of the live-action film series.

Welker claims to have dated actress Pamela Sue Martin and his Tom and Jerry Kids and Droopy, Master Detective co-star Teresa Ganzel.

[12] He is a good friend of his longtime Transformers co-star and fellow voice actor Peter Cullen, in contrast to the rivalry of their respective characters.

[13] A licensed pilot since 2010, Welker flies a Beechcraft Bonanza B36T from a local general aviation airport in Los Angeles County, California.