Greydon Clark was born on February 7, 1943, in Niles, Michigan. He attended Valparaiso University near Chicago and studied acting with coach John Morley. He supported himself as a door-to-door salesman prior to breaking into the movie business.

Clark began his cinematic career as an actor in several enjoyably lowbrow exploitation features for legendary Grade-Z director Al Adamson, giving a memorably offbeat performance as wacky drugged-out biker Acid in the splendidly sleazy Satan's Sadists (1969) (he also wrote the script under the pseudonym Dennis Wayne). Clark also appeared in Hell's Bloody Devils (1970) and the laughably lousy Dracula vs. Frankenstein (1971) for Adamson. Clark has directed an entertainingly diverse array of pleasingly lowbrow low-budget drive-in pictures and straight-to-video offerings from the early 1970s to the late 1990s; they include the trashy blaxploitation double whammies Tom (1973) and Black Shampoo (1976), the silly Satan's Cheerleaders (1977), the nifty sci-fi/horror item Without Warning (1980), the amusing slasher spoof Wacko (1982), the hilariously raunchy Joysticks (1983), the uproariously awful killer mutant cat camp hoot Uninvited (1993), and the especially atrocious Skinheads (1989).

In addition to directing, Clark often writes and produces his own movies and sometimes essays small roles in his films. He both wrote the script and pops up in a minor part in the fun supernatural revenge opus Psychic Killer (1975). His late actress wife Jacqulin Cole appears in several of his films.