The series was announced in October 2004 as a co-production between Marvel Studios and the MoonScoop Group, developed with the intention of shopping it to potential broadcasters.

Unlike the 1994 Fantastic Four animated series, which mostly adapted classic comic book stories directly, World's Greatest Heroes primarily tells original stories while still drawing on elements from various comic iterations and from the live-action film.

Christopher Yost was hired as story editor for the series and worked alongside Craig Kyle to develop it.

Voice actor Sam Vincent voiced multiple characters in the series, including H.E.R.B.I.E., the Trapster, and Peter Parker.

During its original Cartoon Network run, the series suffered from an erratic broadcast schedule, with only 8 of its 26 episodes actually airing.

Cartoon Network briefly revived the show in June 2007 to coincide with the release of the film Fantastic Four: Rise of the Silver Surfer, but this broadcast run was also cut short.

The series was not aired in its complete form until 2009, when Nicktoons picked up the rights and broadcast it alongside Wolverine and the X-Men and Iron Man: Armored Adventures.