One Man's Family debuted as a radio series on April 29, 1932 in Los Angeles, Seattle and San Francisco, moving to the full West Coast NBC network the following month, sponsored by Snowdrift and Wesson Oil. On May 17, 1933, it expanded to the full coast-to-coast NBC network as the first West Coast show heard regularly on the East Coast. The show was broadcast daily in 15 minute installments.

Set in the Sea Cliff area of San Francisco, California, the radio plotline centered around stockbroker Henry Barbour, his wife Fanny and their five children (chronologically: Paul, Hazel, the twins Clifford and Claudia, and Jack).

Over the 27-year run, J. Anthony Smythe starred as Henry Barbour. The first Fanny was Minetta Ellen (1932-35), followed by Mary Adams. Michael Raffeto had the role of author-aviator Paul, but a voice problem led to his replacement in 1955 by Russell Thorson. Hazel was played by Bernice Berwin (1932-58). Beginning in 1932, Barton Yarborough portrayed Clifford, but the character was dropped from the storyline after Yarborough's death from a heart attack on December 19, 1951. Kathleen Wilson introduced the character of Claudia in 1932, continuing in the role until Claudia married in August 1943 and was written out of the story. When Claudia returned (1945-59), she was played by Barbara Fuller. Jack was portrayed by Page Gilman.

The supporting cast in the 1930s and 1940s included Bill Bouchey, Tom Collins, Virginia Gregg, Bill Herbert, Wally Maher, Helen Musselman, Dan O'Herlihy, Walter Paterson, Ken Peters, Frank Provo, Jean Rouverol, Naomi Stevens, Janet Waldo and Ben Wright.

The radio version ran for 3,256 episodes, finally ceasing production on April 24, 1959. (Several sources give the incorrect date of May 8, 1959.)