The heavy-set, stage-trained Pankin began appearing in NYC productions of Shakespeare after receiving his undergraduate degree in 1968. He subsequently appeared in productions at the New York Shakespeare Festival and was a company member at the Vivian Beaumont in 1972. After relocating to the West Coast, Pankin began a career in TV as a supporting player on a number of short-lived series, including "The San Pedro Beach Bums" (ABC, 1977) and "No Soap, Radio" (ABC, 1982), before landing a starring berth on the HBO satirical comedy "Not Necessarily the News" (1983-88). As reporter Bob Charles, Pankin was hilarious in various skits, particularly specializing in slow burns. He also voiced Earl Sinclair, the father, on the ABC sitcom "Dinosaurs" (1991-94).

Pankin made his feature film debut in the all-star bust "Scavenger Hunt" (1979) and followed with other mediocre comic fare ("The Hollywood Knights" 1980; "Dirt Bike Kid" 1986; "Love at Stake" 1987), mixed with the occasional prestige picture ("Fatal Attraction" 1987; "Arachnophobia" 1990). In the 1990s, he continued to alternate between outright misfires ("Mannequin Two: On the Move" 1991 and "Silence of the Hams" 1994) and near misses ("Life Stinks" 1991, "I Love Trouble" (1994) and "Congo" (1995).