The series began on August 25, 1949, on NBC Radio. Set in the Midwest, it starred Robert Young as the General Insurance agent Jim Anderson. His wife Margaret was first portrayed by June Whitley and later by Jean Vander Pyl. The Anderson children were Betty (Rhoda Williams), Bud (Ted Donaldson) and Kathy (Norma Jean Nilsson). Others in the cast were Eleanor Audley, Herb Vigran, and Sam Edwards. Sponsored through most of its run by General Foods, the series was heard Thursday evenings on NBC until March 25, 1954.

On the radio program, the character of Jim differs from the later television character. The radio Jim is far more sarcastic and shows he really rules over his family. Jim also calls his children names, something common on radio but lost in the TV series. For example, Jim says, "What a bunch of stupid children I have." Margaret is portrayed as a paragon of solid reason and patience, unless the plot calls for her to act a bit off; for example, in a Halloween episode, Margaret cannot understand how a table floats in the air. But that is a rare exception.