The real Jim Garrison plays Earl Warren, head of the Warren Commission.

When Joe Pesci is ranting and raving in the hotel room about the assassination, he says that no one will ever solve the JFK murder. He utters the famous line, "It's a mystery wrapped in a riddle inside an enigma...." This was actually first said by Winston Churchill long before JFK was president.

In JFK Wayne Knight plays Numa Bertel. In Seinfeld Wayne Knight plays Newman. In JFK he was used in Jim Garrison's demonstration of the single bullet theory. In Seinfeld he and Kramer told Jerry a story exactly the same as the single bullet theory only that it was spit that hit them not a bullet. Jerry then does the same demonstration that Jim Garrison did in JFK to explain the story. The layout is also the same in both the film and Seinfeld.

In the scene where an FBI agent is harassing one of Garrison's investigators, Bill Brousard, the FBI agent bears a striking resemblance to the real police officer who was also "assassinated" on the same day in Dallas as JFK, Dallas Police Officer J. D. Tippet. It turns out that the actor is Tippet's brother in real life.

In an ET segment at the time of the film's release, Clay Shaw, though a known homosexual, had many friends in business circles and was not known to hold outrageous and elaborate gang bang slumber parties at his house.