Dastmalchian's feature film debut came in the late 2000s, as the Joker’s deranged henchman, Thomas Schiff, in Christopher Nolan's movie The Dark Knight. His turn as Bob Taylor in Denis Villeneuve's Prisoners received strong reviews. Richard Corliss of Time called Dastmalchian's performance "excellent - chatty, modest with some subtle telltale psychopathy" and The Guardian's Paul MacInnes likened his introduction as a new suspect to Kevin Spacey's entrance in Seven.

Other feature film appearances include starring roles in the psychological thriller The Employer, the indie grindhouse hit Sushi Girl, the Detroit-based drama Cass (winner, San Diego Black Film Festival), Girls Will Be Girls 2012 (sequel to the cult hit, Girls Will Be Girls), Saving Lincoln, Virgin Alexander and the Peyton Reed-helmed Marvel Studios film, Ant-Man.

In March 2014, Dastmalchian was awarded the Special Jury Prize for Courage in Storytelling at the South by Southwest Film Festival. He wrote and starred in the feature film Animals, directed by Collin Schiffli. Ashley Moreno of The Austin Chronicle credits Dastmalchian's screenplay with "present[ing] an authenticity often lacking in films about drug abuse." Film Threat's Brian Tallerico similarly sings the praises of Dastmalchian's breakout performance, noting his ability to "capture that sense of self-loathing that comes through in the body language of an addict without overselling it."

On April 2017, he confirmed that he will be returning for Ant-Man and the Wasp.