The series was based on Martin Caidin's 1972 best-selling novel Cyborg, which served as the working title of the show during pre-production.

The producers' first choice to play Steve Austin was actor Monte Markham, before Lee Majors was cast in the role.

The first TV movie adaptation, written by Howard Rodman under the pseudonym Henri Simoun, changed Austin from a colonel in the novel into a civilian astronaut, and omitted the Oscar Goldman character in favor of a supervisor named Oliver Spencer working for the fictional 'OSO'.

The character of Rudy Wells was played by three different actors over the course of the franchise: Martin Balsam in the first pilot, Alan Oppenheimer in later pilots and early seasons, and Martin E. Brooks as the regular from season 3 onward.

Sandra Bullock appeared in an early role as a new bionic woman in the 1989 TV movie Bionic Showdown: The Six Million Dollar Man and the Bionic Woman.

The crash footage used in the opening credits is real archival footage from the actual M2-F2 lifting body crash of test pilot Bruce Peterson on May 10, 1967, who survived the accident at roughly 260 mph but later lost an eye to infection.

The two later pilot TV movies used a theme song written by Glen A. Larson and sung by Dusty Springfield, which was replaced by an instrumental theme composed by Oliver Nelson once the weekly series began.

The show's iconic electronic 'dit dit dit dit' sound effect used for bionic feats was actually first used in the season 1 episode 'Day of the Robot' for a robotic clone character, before becoming associated with Austin's bionics; the slow-motion technique was reportedly inspired by its use in NFL Films rather than the martial arts show Kung Fu, despite being nicknamed 'Kung Fu slow motion' at the time.

In Brazil under the military dictatorship, government officials appointed rather than elected were nicknamed 'bionic' (biônicos) due to the show's popularity, a term used until such appointments were abolished by the 1988 Constitution.

In Israel, the series was retitled The Man Worth Millions because the phrase 'six million' evoked painful memories of the Holocaust.

A feature film adaptation went through decades of development hell, with a 1995 Kevin Smith screenplay, a scrapped Jim Carrey comedic take directed by Todd Phillips, and later a Mark Wahlberg-led version that saw directors Peter Berg, Damian Szifron, and Travis Knight attached before ultimately stalling without a release date as of 2023.