Leto's casting comes after Hefner's death Wednesday of natural causes at the age of 91.
Ratner had announced in April that he was developing a biopic on the magazine mogul through his RatPac Entertainment studio after optioning Hefner's life rights, Variety reported. Hefner was signed on as an executive producer and had given the project his blessing.
"In recent years there has been plenty of interest and much conversation about doing a feature film based on my life. I have always believed that when the timing was truly right, the perfect creative partners would come together for this project. I believe we've found those partners in Brett Ratner and RatPac Entertainment. I'm very much looking forward to this collaboration," Hefner said at the time.
Also in April, Ratner had invited Leto to the Playboy Mansion for the premiere of Amazon documentary series, American Playboy: The Hugh Hefner Story.
"Jared is an old friend," Ratner said to The Hollywood Reporter about the actor. "When he heard I got the rights to Hef's story, he told me, 'I want to play him. I want to understand him.' And I really believe Jared can do it. He's one of the great actors of today."
Leto will be seen opposite Ryan Gosling and Harrison Ford in Blade Runner 2049, due in theaters on Friday. Leto is also set to once again portray DC Comics villain The Joker in a sequel to Suicide Squad and in a new film that will co-star Margot Robbie as The Joker's girlfriend Harley Quinn.