His first performances were in vaudeville, at which point he legally changed his last name to the easier-to-pronounce "Bergen". He also worked in one-reel movie shorts, but his real success was on the radio. He and Charlie were seen at a New York party by Elsa Maxwell for Noël Coward, who recommended them for an engagement at the famous Rainbow Room. It was there that two producers saw Bergen and Charlie perform. They then recommended them for a guest appearance on Rudy Vallée's program. Their initial appearance, on December 17, 1936, was so successful that the following year they were given their own show, as part of The Chase and Sanborn Hour. Under various sponsors (and two different networks), they were on the air from May 9, 1937 to July 1, 1956. The popularity of a ventriloquist on radio, when one could see neither the dummies nor his skill, surprised and puzzled many critics, then and now. Even knowing that Bergen provided the voice, listeners perceived Charlie as a genuine person, but only through artwork, rather than photos, could the character be seen as truly lifelike. Thus, in 1947, Sam Berman caricatured Bergen and McCarthy for the network's glossy promotional book, NBC Parade of Stars: As Heard Over Your Favorite NBC Station.

It was Bergen's skill as an entertainer and vocal performer, and especially his characterization of Charlie, that carried the show. Many of the shows have survived and are available for audiences today to experience the phenomenon firsthand. Bergen's success on radio was paralleled in the United Kingdom by Peter Brough and his dummy Archie Andrews (Educating Archie).

Sam Berman's caricature of Charlie McCarthy and Edgar Bergen for NBC's 1947 promotion book

For the radio program, Bergen developed other characters, notably the slow-witted Mortimer Snerd and the man-hungry Effie Klinker. The star remained Charlie, who was always presented as a highly precocious child (albeit in top hat, cape, and monocle) – a debonair, girl-crazy, child-about-town. As a child, and a wooden one at that, Charlie could get away with double entendre which were otherwise impossible under broadcast standards of the time.