Lou Ferrigno, who played the Hulk in the live-action TV series from 1978 to 1982, provided the character's voice in this animated series.

UPN decided that the first season was too dark, so for season two the network mandated a lighter tone and ordered that She-Hulk become a regular co-star, leading the series to be officially renamed 'The Incredible Hulk and She-Hulk'.

Showrunner Tom Tataranowicz was chosen after successfully retooling the second seasons of Marvel Action Hour's Fantastic Four and Iron Man, and he described his intention for the show as being 'more like drama with action than action with drama'.

Like the original 1978 live-action series, the show drew inspiration from The Fugitive, focusing on Bruce Banner on the run from General Thunderbolt Ross and the Hulkbusters while seeking a cure.

The first season included a guest appearance by Ghost Rider intended as a potential backdoor pilot for a companion series that would also air on UPN.

Several actors reprised their roles from other Marvel Action Hour cartoons, including Dorian Harewood as War Machine and Robert Hays as Tony Stark/Iron Man from the Iron Man series, and Beau Weaver and Chuck McCann as Mister Fantastic and The Thing from the Fantastic Four series, tying the shows into a shared continuity.

The second season won an Emmy Award for 'best audio editing' for its work on the episode 'The Lost Village'.

Network mandates for season two included toning down the sexuality of She-Hulk's character to make her more of a sassy counterpart rather than the more risqué portrayal originally intended.