When HBO first pitched a Spawn animated series, other networks had already expressed interest thinking it could work as a Saturday-morning cartoon, not realizing the comic's content was aimed at an adult audience.

Todd McFarlane told HBO executives during his initial pitch meeting that he wanted to know if he could say the word 'fuck', reasoning that if they allowed that, he could get away with a hundred other things too.

HBO Animation, a newly created division intended to focus on adult animation, produced Spawn as its first project, co-producing it with Todd McFarlane Entertainment while McFarlane commuted weekly from Phoenix to Century City for three years.

Composer Shirley Walker, who had previously scored Batman: The Animated Series, was recruited by producer Eric Radomski to give Spawn a more organic, subtle electronic soundtrack rather than traditional orchestral music.

South Korean studio Koko Enterprises animated the series while simultaneously working on family-friendly cartoons, leading to recurring issues where blood was rendered looking like honey and had to be redone, and the animators struggled to understand the show's intentional use of dark shadows.

Pearl Jam frontman Eddie Vedder was such a fan of the show that he recorded episodes onto VHS and edited the song 'Do the Evolution' over Spawn footage using Avid software, then sent the tape to Todd McFarlane, which led to McFarlane directing the official music video in the same animated style.

St. Louis Blues hockey player Tony Twist filed a successful lawsuit against HBO and Todd McFarlane Entertainment after discovering a mob boss character in the first season was named after him and depicted in compromising and violent scenarios; as a result the character was never used again and was renamed 'Vito Gravano' in comic reprints.

The live-action introductions hosted by Todd McFarlane were filmed in a style similar to R. L. Stine's Goosebumps intros, and the first season's segments were directed by future Hollywood filmmaker Doug Liman, who at the time was roommates with an HBO executive.

A lawsuit between Todd McFarlane and comic writer Neil Gaiman over the character Angela, who appeared briefly in the fourth episode of season one, prevented the character from being used again despite the writers considering bringing her back before the show's cancellation.