Though the cast ultimately proved to be one of the film's greatest strengths, director William Friedkin had problems with casting choices from the start. He was strongly opposed to the choice of Gene Hackman for the lead, and actually first considered Paul Newman (out of the budget range), then Jackie Gleason, Peter Boyle and a New York columnist, Jimmy Breslin, who had never acted before. However, Gleason, at that time, was considered box-office poison by the studio after his film "Gigot" (1962) had flopped several years before, Boyle declined the role after disapproving of the violent theme of the film, and Breslin refused to get behind the wheel of a car, which was required of Popeye's character for an integral car chase scene. Steve McQueen was also considered, but he did not want to do another police film after "Bullitt" (1968) and, as with Newman, his fee would have exceeded the movie's budget. Tough guy Charles Bronson was also considered for the role. Lee Marvin, James Caan, and Robert Mitchum were also considered for the role, all of whom turned it down. Friedkin almost settled for Rod Taylor (who had actively pursued the role, according to Hackman), another choice the studio approved, before he went with Hackman.
The casting of Fernando Rey as the main French heroin smuggler, Alain Charnier (irreverently referred to throughout the film as "Frog One"), resulted from mistaken identity. Friedkin had seen Luis Buñuel's 1967 French film "Belle de Jour" and had been impressed by the performance of Francisco Rabal, who had a small role in the film. However, Friedkin did not know his name, and remembered only that he was a Spanish actor. He asked his casting director to find the actor, and the casting director instead contacted Rey, a Spanish actor who had appeared in several other films directed by Buñuel. After Rabal was finally reached, they discovered he spoke neither French nor English, and Rey was kept in the film. After screening the film's final cut, Rey's French was deemed unacceptable by the filmmakers. They decided to dub his French while preserving his English dialogue.
In an audio commentary track recorded by Friedkin for the Collector's Edition DVD release of the film, Friedkin notes that the film's documentary-like realism was the direct result of the influence of having seen "Z" (1969), a French film by Costa-Gavras. Friedkin mentioned the film's influence on him when directing "The French Connection": "After I saw 'Z', I realized how I could shoot 'The French Connection'. Because (Costa-Gravas) shot 'Z' like a documentary. It was a fiction film but it was made like it was actually happening. Like the camera didn't know what was gonna happen next. And that is an induced technique. It looks like he happened upon the scene and captured what was going on as you do in a documentary. My first films were documentaries too. So I understood what he was doing but I never thought you could do that in a feature at that time until I saw 'Z'."
Friedkin credits his decision to direct the movie to a discussion with film director Howard Hawks, whose daughter was living with Friedkin at the time. Friedkin asked Hawks what he thought of his movies, to which Hawks bluntly replied that they were "lousy." Instead Hawks recommended that he "Make a good chase. Make one better than anyone's done."

And so he did.