Serling served in the U.S. Army during World War II and began writing scripts for Cincinnati radio and television stations while a student at Antioch College in Yellow Springs, Ohio (B.A., 1950). In 1951 he began selling television dramas to live network series and quickly became one of the medium's leading writers: over the next four years, he sold 90 freelance scripts. He won a 1955 Emmy Award for his script Patterns, a story of ruthless business executives, and a 1957 Emmy for his script Requiem for a Heavyweight. Serling's dramas were often controversial, and despite his protests such scripts as A Town Has Turned to Dust (1958), about lynching, and The Rank and File (1959), about labour-union corruption, were extensively revised by CBS-TV censors.

Tired of battling censors, Serling abandoned writing realistic scripts in order to produce and narrate a science-fiction anthology series The Twilight Zone (1959–64); for this he won a third writing Emmy, in 1959. He also wrote screenplays, often based on his television scripts, such as Patterns (1956) and The Rack (1956). He was also coauthor of The Planet of the Apes (1968). Among his later projects were hosting a 1970–73 fantasy anthology series, Rod Serling's Night Gallery, and teaching dramatic writing at Ithaca College in New York.