The Cuphead Show! was developed by Dave Wasson for Netflix based on the 2017 video game Cuphead by Studio MDHR, with the game's creators Chad and Jared Moldenhauer serving as executive producers.

Netflix ordered a total of 36 episodes to be produced, which ended up being released across three seasons rather than a single large season.

The series was animated by Lighthouse Studios, a Kilkenny-based division between Mercury Filmworks and Cartoon Saloon, while stop motion animation was provided by Screen Novelties.

To meet streaming series deadlines, the production crew were unable to use hand-drawn animation like in the original game, and instead used puppet-based methods while incorporating elements to match the 1930s rubber hose animation style.

The show's music was composed by Ego Plum, which was announced when the series was first revealed at the Annecy International Animation Film Festival in June 2020.

In July 2025, series writer Deeki Deke expressed interest in a crossover between Cuphead and Hazbin Hotel, joking that it would 'ignite a holy war between the fandoms' since holy wars are embedded in both shows' backstories.

The release of The Cuphead Show! led to a noticeable, consistent uptick in sales of the Cuphead video game even before the release of its downloadable content, according to creator Chad Moldenhauer.

In June 2024, fans launched the '#RenewTheCupheadShow' social media campaign to advocate for the series' return after its cancellation.