Milius wrote, co-wrote and/or directed such popular and critically acclaimed films such as Apocalypse Now, The Hunt for Red October, Big Wednesday, Dillinger, Flight of the Intruder, and The Wind and the Lion. He is also well-known as the director of Red Dawn, a controversial 1984 film premised on a fictional Soviet invasion of the United States.

A self-styled "Zen anarchist", Milius is a member of the Board of Directors of the National Rifle Association, an avid gun collector and a strong opponent of gun control laws.

Red Dawn was again in the news in December, 2003 in connection with the capture of the former Iraqi dictator Saddam Hussein. The American commander of the operation to capture Hussein was a fan of Milius' film, causing him to call the military operation which captured Saddam Hussein Operation Red Dawn. He also dubbed the military units who actually captured Hussein "Wolverine One" and "Wolverine Two" after the fictional "Wolverines" unit in Red Dawn.

Milius is also known as the director of the film Conan the Barbarian, which made a star out of the (then) relatively unknown actor and body builder Arnold Schwarzenegger. Milius also contributed to the famous USS Indianapolis monologue for the film Jaws, and suggested to Steven Spielberg the "bookend" scenes in the military graveyard in Normandy which were used at the beginning and end of Saving Private Ryan, and coined the famous "make my day" and "do you feel lucky?" lines from the Dirty Harry movies.

Director George Lucas was inspired by his friend and mentor Milius to create the "John Milner" character as the protagonist of his celebrated film American Graffiti.

Milius is also reportedly the inspiration behind the Walter Sobchak character (played by John Goodman) in the film The Big Lebowski.