Welker's first on camera film role was as a bar fight participant in Stan Dragoti’s 1972 film Dirty Little Billy. His next film role was in The Trouble with Girls, portraying a college kid from Rutgers University who befriends Elvis Presley. He later co-starred with Don Knotts in Universal's How to Frame a Figg. Welker also appeared in two Disney films, The Computer Wore Tennis Shoes, and Now You See Him, Now You Don't. His on camera television appearances included roles in Love American Style, The Partridge Family, and The Don Knotts Show. He played a prosecutor in 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 also appeared on Laugh In, The Dean Martin Roast, The Mike Douglas Show, The Tonight Show, Merv Griffin, The Smothers Brothers Show, The Burns and Schreiber Comedy Hour, Laugh Trax, and as one of the cast members in the 1985 special of That Was the Year That Was with David Frost. In the latter show, he appeared alongside Jim Staahl and Howie Mandel. Frank also played an on camera role of a voice actor on an episode of Simon & Simon and in the film The Informant as Matt Damon's father.

Welker is the voice of both Fred Jones and Scooby-Doo