Pankin was born in Philadelphia, Pennsylvania, on April 8, 1946. He attended Dickinson College, where he was a member of Sigma Alpha Epsilon, and Columbia University.
Early in his career, Pankin frequently performed at St. Vincent Summer Theatre and still returns to perform there often. Pankin is known for his portrayal as anchor Bob Charles on HBO's Not Necessarily the News, as well for voicing Earl Sinclair in the family sitcom Dinosaurs, he is also known for playing the father Mike Dooley on the short-lived sitcom Nearly Departed. Pankin also played an Orthodox Jew in Curb Your Enthusiasm. Pankin made many guest appearances and lent his voice to animated shows, as well for appearing in numerous television commercials.
One of Pankin's earliest film appearances was as asthmatic musician/magician Dudley Laywicker in Hollywood Knights. Among his approximately three dozen film appearances, he starred in Zenon: Girl of the 21st Century, Zenon: The Zequel, and Zenon: Z3 as Commander Plank. He also appeared in Honey, We Shrunk Ourselves, as the brother of Wayne Szalinski, and also co-starred as a bossy, self-important lawman in the horror/comedy Arachnophobia.

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