[4] From 1964 to 1968, he studied Graphic Design at Portland State University, where he was a member of the film society and worked on the yearbook.

[5] Plympton's illustrations and cartoons have been published in The New York Times and the weekly newspaper The Village Voice, as well as in the magazines Vogue, Rolling Stone, Vanity Fair, Penthouse, and National Lampoon.

His political cartoon strip Plympton, which began in 1975 in the SoHo Weekly News, eventually was syndicated and appeared in over 20 newspapers.

[7] In 1991, Plympton won the Prix Spécial du Jury at the Cannes Film Festival for Push Comes to Shove which was featured on MTV's animated series Liquid Television.

The actress Martha Plimpton, a distant relative of his,[10] served as associate producer on Plympton's animated feature Hair High (2004), doing much of the casting.

Plympton contributed animation to the 2006 History Channel series 10 Days That Unexpectedly Changed America, to illustrate the events of Shays' Rebellion.

[18] The archive has preserved Plympton's films such as Your Face, The Tune, Guard Dog, and The Cow Who Wanted to Be a Hamburger.

[1] Plympton has stated he has many influences, the biggest being the work of the Walt Disney studio with others including Tex Avery, Bob Clampett, Robert Crumb, Milton Glaser, Charles Addams, Roland Topor, Quentin Tarantino, Frank Capra, Richard Lester, Bob Godfrey, Saul Steinberg, Tomi Ungerer, Jacques Tati,[27] Milt Kahl,[28] Carlos Nine, and Jules Feiffer.