Ben Casey was based on real-life neurosurgeon Dr. Allan "Max" Warner. Dr. Warner later changed his specialty to psychiatry, because he believed that his association with the show prevented him from being a board certified neurologist.

The five symbols written on the blackboard at the start of each episode represent man, woman, birth, death, and infinity.

Sam Jaffe (Dr. David Zorba) left the show due to conflicts with Vince Edwards (Dr. Ben Casey). Guest star Sammy Davis, Jr. and Director Jerry Lewis also had conflicts with Edwards.

According to Director Mark Rydell, Vince Edwards had a gambling problem. Edwards demanded to film all of his scenes first, so that he could leave the set and go to a racetrack. According to Harry Landers, Edwards also constantly asked the cast and crew for money, with which to gamble, and leave the set for hours at a time.

Cliff Robertson and Jack Lord turned down the role of Ben Casey.

Bettye Ackerman (Dr. Maggie Graham) was married to Sam Jaffe (Dr. David Zorba) in real-life.

According to Harry Landers (Dr. Ted Hoffman), Franchot Tone (Dr. Daniel Niles Freeland) was constantly drunk on the set. In episodes which Landers directed, he always had Tone sitting down to stop him from swaying.

Dr. Ben Casey was a neurosurgeon.

Russell Johnson tried out for the role of Dr. Ben Casey, but wasn't chosen. He next auditioned for the part of Professor Roy Hinkley on Gilligan's Island (1964), and got it.

Dr. Zorba was originally named "Dr. Rosenberg". But ABC insisted his name to be changed, because they did not want the character to be Jewish. Creator James E. Moser cast Sam Jaffe to play Zorba with a Yiddish accent to emphasize that the character was meant to be Jewish.