Memory of a Killer is based on the 2003 Belgian film De Zaak Alzheimer and the 1985 novel of the same name.

Fox gave the production a straight-to-series order on May 12, 2025, before it was later renewed for a second season in April 2026.

The show's production went through significant showrunner changes: David Schulner joined as executive producer and co-showrunner in July 2025, but by November 2025 he and original creators Ed Whitmore and Tracey Malone stepped down as co-showrunners and were replaced by Aaron Zelman and Glenn Kessler.

Patrick Dempsey was cast as lead Angelo Doyle at the time of the series order announcement, and he also serves as an executive producer on the show.

Michael Imperioli, Richard Harmon, and Odeya Rush joined the cast as series regulars in July 2025, followed by Daniel David Stewart and Peter Gadiot in starring roles in August 2025.

Michaela McManus and Gina Torres joined the cast in recurring roles in September 2025.

Principal photography took place entirely in Toronto, Ontario, Canada, running from August 18, 2025 to February 9, 2026.

The series received mixed reviews, holding a 50% approval rating on Rotten Tomatoes from 12 critics and a Metacritic score of 58 out of 100 based on 9 critics.