The series began as a pilot ordered by HBO Max in September 2021 as a potential spin-off of Doom Patrol, with Steve Yockey as writer and executive producer.

After being greenlit at HBO Max in April 2022, the project moved to Netflix in February 2023, reportedly because it was incompatible with DC Studios co-CEOs James Gunn and Peter Safran's plans to set HBO Max's DC shows in the DC Universe, and because HBO Max could not air it before 2024.

While the show was still developed for HBO Max, Warner Bros. did not allow the producers to use elements from The Sandman to avoid licensing issues with Netflix, so showrunners only included broad, subtle connections between the two shows despite always intending them to share continuity.

Ruth Connell, who plays the Night Nurse, had already portrayed the same character in the Doom Patrol episode 'Dead Patrol,' which marked the first TV appearance of the Dead Boy Detectives.

Alexander Calvert was originally cast in November 2021 but was replaced by Lukas Gage as the Cat King in September 2022.

Kirby's cameo as Death, reprising her role from The Sandman, was added to the pilot after the series moved to Netflix; in the original HBO Max version, Death was meant to appear only offscreen due to licensing issues.

The pilot episode was filmed between December 2021 and January 2022, directed by Lee Toland Krieger, while the full series was shot from November 7, 2022 to April 5, 2023 in Langley, British Columbia.

Following its cancellation by Netflix in August 2024 after one season, fans launched the 'Save Dead Boy Detectives Campaign' on Tumblr and Twitter, crowdfunding billboards in Los Angeles and New York City and gathering over 24,000 petition signatures for renewal.