Fox entered into a public feud with Bay following comments made in a 2009 interview with Wonderland Magazine, in which she claimed Bay behaved like "a tyrant" on set and compared him to Adolf Hitler.
The actress was dismissed from Transformers: Dark of the Moon and replaced by Rosie Huntington-Whiteley.
Speaking to the Toronto Star, O'Dowd branded Bay an "asshole" and "sexist" for his treatment of Fox.
"It's one of the sexist things I've ever seen. She called him an asshole. Well, he is a f**king asshole. She's not the only one who has said that. Why has she been singled out?"
O'Dowd admitted that he is not a fan of Bay's film work, adding: "I would never f**king watch his films, never mind go and act in them."
Watch Chris O'Dowd and Megan Fox in the trailer for Friends with Kids below: