Wally Cox starred as Robinson J. Peepers, Jefferson City's junior high school science teacher.

Others in the cast included Tony Randall as history teacher Harvey Weskit; Georgiann Johnson as Harvey's wife, Marge; Patricia Benoit as school nurse Nancy Remington; Marion Lorne as oft-confused English teacher Mrs. Gurney; Jack Warden as athletic coach Frank Whip; and Ernest Truex and Sylvia Field as Nancy's parents.

In a typical scene, Peepers sees a hopscotch grid chalked on a sidewalk, and thinking himself alone, plays the game with abandon, only to discover that his girlfriend Nancy has been silently watching the entire time.

By February 1954, though, the couple's romance had progressed to the point of Mr. Peepers presenting Nancy with a photograph of himself, inscribed "Scientifically yours, Robinson".

[5] Mister Peepers was aired live, on stage before an audience at the New Century Theatre, 932 7th Avenue, New York City—preserved in the form of 16 mm kinescopes.

In 2005, the first 26 episodes of Mister Peepers, which had been preserved by the UCLA Film and Television Archive, were released on DVD by S'more Entertainment.

The tagline at the bottom of the box reads: "America's Favorite Science Teacher, Underdog and All-Round Nice Guy."