As a direct result of the front-page headlines Orson Welles generated with his 1938 Halloween production "The War of the Worlds", Campbell's Soup signed on as sponsor.

The series made its debut with Welles's adaptation of Rebecca, with guest stars Margaret Sullavan and Mildred Natwick.

The radio drama was the first adaptation of the 1938 novel by Daphne Du Maurier; the author was interviewed live from London at the conclusion of the broadcast.

[5]: 175–176 After signing a film contract with RKO in August 1939, Welles began commuting from Hollywood to New York for the two Sunday broadcasts of The Campbell Playhouse.

[1]: 353 Screenwriter Herman J. Mankiewicz was put on the Mercury payroll and wrote five scripts[6] for Campbell Playhouse shows broadcast between November 12, 1939, and March 17, 1940.

[9] One notable dispute came after the broadcast of "Algiers", which employed a carefully crafted tapestry of sound to create the world of the Casbah.

After the broadcast of March 31, 1940—a reprise of Jane Eyre, after Welles's suggestion of Alice Adams was not accepted—Welles and Campbell parted amicably.

The series' focus shifted away from classic play and novel adaptations to lighter, more popular fare, still with casts drawn from the ranks of film actors.