In 1952, Ed Wood is struggling to join the film industry. Upon hearing of an announcement in Variety magazine that producer George Weiss is trying to purchase Christine Jorgensen's life story, Ed wants to meet Weiss. Weiss explains that Variety's announcement was a news leak, and it is impossible to purchase Jorgensen's rights. The producer decides to fictionalize the film, titled I Changed My Sex!. Ed tries to convince Weiss that he is perfect to direct the film because he is a transvestite, but is unsuccessful since Weiss wants a director with experience. Ed meets his longtime idol Bela Lugosi and the two become friends. Wood persuades Weiss to let him direct the film by convincing him that having a star in the film would sell tickets, and they could sign Bela for a low price.
Ed and Weiss argue over the film's title and subject matter: Weiss has the poster printed, which Ed changes to Glen or Glenda and writes the film about a transvestite rather than a sex change. Weiss allows Ed to shoot whatever he wants as long as the film meets the required length. Ed takes to film production with an unusual approach; shooting only one take per scene, giving actors very little direction and using stock footage to fill in gaps. The movie is released to critical and commercial failure. Because of this, Ed is unsuccessful in getting a job at Screen Classics, but Ed's girlfriend, Dolores Fuller, tells him that he should try financing his next film independently. Ed is unsuccessful in finding money for Bride of the Atom, but is introduced to the psychic The Amazing Criswell who gives him advice on how to sell himself better.
Ed meets Loretta King, who he thinks has enough money to fund Bride of the Atom and ends up casting her as the lead instead of Dolores as planned. Filming begins, but is halted when it is revealed that Loretta is actually poor, and Ed has no money to continue production. Ed convinces meat packing industry tycoon Don McCoy to take over funding the film, who agrees as long as the film stars his son Tony as the leading man and the film ends with an explosion. The filming finishes with the title being changed to Bride of the Monster, but Dolores breaks up with Ed after the wrap party because of his circle of friends, his work, and transvestism. Bela attempts to conduct a double suicide with Ed after the government cuts off his unemployment, but is talked out of it. Bela checks himself into rehab, and Ed meets Kathy O'Hara, who is visiting her father there. Ed takes her on a date and reveals to her his transvestism, which she accepts.
Ed shoots a film with Bela outside his home. When Ed and company attend the premiere for Bride of the Monster, an angry mob chases them out of the theater. Bela passes away, leaving Ed without a star. Ed convinces a church leader named Reynolds that funding Ed's script for Grave Robbers from Outer Space would result in a box office success, and generate enough money for Reynolds' dream project. Dr. Tom Mason, Kathy's chiropractor, is chosen to be Bela's stand-in for resembling Lugosi. Ed and the Baptists have conflicts over the title and content of the script which they want to have changed to Plan 9 from Outer Space, along with Ed's B movie directing style, his casting decisions and his transvestism. Ed leaves the set to go to the nearest bar, where he encounters his idol, Orson Welles. Filming for Plan 9 finishes with Ed taking action against his producers. Plan 9 is premiered and Ed and Kathy go to Las Vegas to get married.

Question: Why does Dolores break up with Ed?
Answer: She can't handle his transvestitism.
Alternative answer: She does not like his friends, work and the fact that he is a transvestite.