NBC commissioned the pilot in August 2022, with production taking place shortly before the 2023 Writers Guild of America strike, and the show was given an official series order in June 2023.

Due to strike-related production delays, St. Denis Medical was pushed from its original planned debut to the 2024–25 television season, with NBC confirming a fall 2024 air date in May 2024.

Wendi McLendon-Covey was confirmed to lead the series as Joyce as soon as the pilot was commissioned, while Allison Tolman was cast as Alex in March 2023.

David Alan Grier, Josh Lawson, Mekki Leeper and Kahyun Kim were all confirmed as series regulars in March 2023, before the pilot even began filming.

NBA player Draymond Green made a guest appearance in season 2 as the 'Lightning Patient'.

On Rotten Tomatoes the series holds an 81% approval rating based on 27 critic reviews, while Metacritic gave it a weighted score of 66 out of 100 based on 16 critics, indicating 'generally favorable' reviews.

The premiere episode was the top-rated scripted show of the night and the highest-rated scripted broadcast series launch in nearly two years without an NFL lead-in; its total audience grew 85% in cross-platform viewing the following week to 7.4 million viewers, with the key demographic rating up 182% to 1.44.

In the United Kingdom the series was acquired by the BBC in March 2024, with season one first launching on BBC iPlayer on June 6, 2025 before a later linear premiere on BBC One the same evening.