The producers of the show were Martin Manulis, John Houseman, Russell Stoneman, Fred Coe, Arthur Penn, and Hubbell Robinson.

With Alex North's opening theme music, the series debuted October 4, 1956, with Rod Serling's adaptation of Pat Frank's novel Forbidden Area starring Charlton Heston.

The following week, Requiem for a Heavyweight, also scripted by Serling, received critical accolades and later dominated the 1956 Emmys by winning awards in six categories, including best direction, best teleplay and best actor.

[4] Writers for the series included Robert Alan Aurthur, Rod Serling, Whitfield Cook, David E. Durston, Sumner Locke Elliott, Horton Foote, Frank D. Gilroy, Roger O. Hirson, A. E. Hotchner, Loring Mandel, Abby Mann, J. P. Miller, Jack E. Miller, Paul Monash, and Leslie Stevens.

As Playhouse 90 moved into 1957, Frankenheimer directed a science fiction drama, The Ninth Day (January 10, 1957), by Howard and Dorothy Baker, about a small group of World War III survivors, and a Serling adaptation, The Comedian (February 14, 1957), based on the short story by Ernest Lehman, and starring Mickey Rooney as an abrasive, manipulative television comedian.

Frankenheimer ended the year with The Thundering Wave (December 12, 1957), starring James and Pamela Mason in an Aurthur drama about an acting couple who agree to do a play together despite their separation.

Frankenheimer kicked off 1958 with The Last Man (January 9, 1958), an Aaron Spelling revenge drama, followed by The Violent Heart (February 6, 1958) from the Daphne du Maurier story of romance on the French Riviera, Rumors of Evening (May 1, 1958) about a World War II pilot obsessed with a USO entertainer, and Serling's Bomber's Moon (May 22, 1958) about a World War II pilot accused of cowardice.

Face of a Hero (January 1, 1959), based on the Pierre Boulle novel, starred Jack Lemmon, who took this play to Broadway for a run of 36 performances during October to November 1960.

The following year, Frankenheimer began with The Blue Men (January 15, 1959), an Alvin Boretz drama about the trial of a police detective who refused to make an arrest.

Kevin Dowler, writing for the Museum of Broadcast Communications, noted: Normally, the program was telecast in black-and-white, but on Christmas night, 1958, it offered a color production of Tchaikovsky's The Nutcracker, starring the New York City Ballet and choreographed by George Balanchine.

[8][9] Several teleplays in the series were filmed later as theatrical motion pictures, including Requiem for a Heavyweight, The Helen Morgan Story, Days of Wine and Roses, and Judgment at Nuremberg.