Code Black is based on a 2013 documentary film of the same name by Dr. Ryan McGarry, which depicted the real-life historic Los Angeles County General Hospital, one of the busiest trauma centers in the United States. McGarry went on to serve as an executive producer on the TV series.

Maggie Grace was originally cast as the lead, Dr. Leanne Rorish, but left the show before filming began; Marcia Gay Harden, who had first been cast as Christa, then took over the role of Rorish, and Bonnie Somerville was brought in to play Christa instead.

Luis Guzman's character was originally announced as senior nurse 'Jose Santiago' before being renamed 'Jesse Salander'.

Rob Lowe joined the main cast at the start of season 2 as Colonel Ethan Willis, a Combat Casualty Care physician assigned to the ER through a U.S. Army training program.

Moon Bloodgood was originally cast in a recurring role as paramedic Rox Valenzuela for season 3 and was promoted to series regular by the fourth episode, following the departures of Melanie Chandra and Jillian Murray.

The pilot episode was actually filmed at the decommissioned original Los Angeles County General Hospital facility, which has since been converted into mixed-use office space.

For the series, production designer Richard Toyon photographed the real hospital extensively and rebuilt a full replica of the facility at the Walt Disney Studios in Burbank.

To avoid the typical pristine look of medical dramas, the crew deliberately aged the set with layers of fake dirt and wear, even spilling fake blood on the floor tiles and wiping it up to leave stains between them for a lived-in look.

The set featured a corkboard drop ceiling matching the real hospital, which meant the crew couldn't use overhead lighting rigs and instead relied on practical on-set lighting, including four vintage operating-room lights combined into one working fixture, compensating with digital cameras for lower light levels.

Many props and set pieces—including gurneys, beds, lights, X-ray holders, clipboards, and textbooks from different eras—were bought as surplus directly from L.A. County General Hospital, while outdated health posters and misspelled signage were created in-house.

Creator Michael Seitzman wanted to visualize the concept of a 'Code Black' emergency directly for audiences, so the production team built a fictional prop called the 'Code-Black-ometer,' made from old push-button consoles and Chevy taillights, which lit up through stages from green to yellow to red to black.