Adam-12 was created by Robert A. Cinader and Jack Webb and produced in cooperation with the actual LAPD, similar to Webb's other shows Dragnet and Emergency!, in an effort to realistically depict police procedures and jargon.

The show's first episode, 'Log 1: The Impossible Mission', was filmed in September 1967, a full year before the pilot was officially picked up for series.

Driving scenes were filmed on public streets using a camera platform with three remote-controlled cameras mounted on the cruiser's hood, which was towed by a station wagon; a script supervisor lay on the car floor to read police radio dialogue while the director and sound man rode in a rear-facing seat in the towing wagon.

For the pilot, Jack Webb disliked windshield sky reflections obscuring the actors, so the windshield was removed, but this caused hair-blowing and audio problems; the crew's solution was to reinstall the windshield and add an overhead shield and side panels forming an open-ended 'black box' over the front of the car.

The series used the real Rampart Police Station at 2710 West Temple Street as its filming location; the building, opened in 1966, was later renovated and reopened in 2016 as the LAPD Metropolitan Division Facility.

In 1974, during production of the seventh season, Martin Milner left temporarily to star in The Swiss Family Robinson, prompting producers to test Jo Ann Pflug, Mark Harmon, and Michael Warren as potential replacements, while another plan considered replacing Malloy entirely with Gary Crosby's character Ed Wells for a planned eighth season.

The planned eighth season was ultimately scrapped after Kent McCord left the show following the birth of his son just three days before the seventh season finale aired, forcing the series to end after seven seasons.

Shaaron Claridge, who voiced the police dispatcher in nearly every episode, was an actual LAPD dispatcher who did the show as a side job until her retirement in 1990.

The police cars used real vehicles purchased from local dealerships and outfitted to accurate LAPD specifications, and the slang police nickname '12' likely originated from the show's title, similar to how 'five-O' came from Hawaii Five-O.

In 2003, the real LAPD activated an actual patrol unit with the call sign '1-Adam-12' in Central Division, reserved only for officers who demonstrated outstanding duty performance.

The 1-Adam-12 call sign can be heard over a police radio in The Matrix Reloaded, and the same call sign is used for an AD Police helicopter in a 1987 episode of the anime Bubblegum Crisis.

Martin Milner's real children Andrew and Amy Milner both appeared in episodes, with Andrew serving as stunt double for a guest actor in a minibike chase scene, and Kent McCord's real daughter Kristen also appeared as a child extra in a later episode.