Early cover illustrations were by Feldstein. Wally Wood took over as the regular cover illustrator in 1952. Wood was also the most dominant artist in the title, and for a period of time in 1952 did two stories per issue. The stories were drawn by Feldstein, Frank Frazetta, Al Williamson, Joe Orlando, George Evans, Harvey Kurtzman, George Roussos, Harry Harrison, Will Elder, Jack Kamen, Sid Check and Jack Olesen.
The companion comic for Weird Science was Weird Fantasy. The two titles merged in 1954 to become Weird Science-Fantasy due to poor sales. Weird Science-Fantasy ran for seven issues before a title change to Incredible Science Fiction for four issues.
Weird Science featured a number of Ray Bradbury adaptations after he and EC came to an agreement in 1952. These stories included "The Long Years" (#17), "Mars is Heaven" (#18), "The One Who Waits" (#19), "Surprise Package" (#20), "Punishment Without Crime" (#21) and "Outcast of the Stars" (#22).