In 1999, Puri acted in a Kannada movie A.K. 47 as a strict police officer who tries to keep the city safe from the underworld which went on to become a huge commercial hit. Puri's acting in the movie is very memorable. He has rendered his own voice for the Kannada dialogues. In the same year, he starred in the successful British comedy film East is East, where he played a first generation Pakistani immigrant in the north of England, struggling to come to terms with his far more westernised children.

Puri also had a cameo in the highly acclaimed film Gandhi (1982, directed by Richard Attenborough). In the mid-1990s, Puri diversified to play character roles in mainstream Hindi cinema, where his roles are more tuned to mass audiences than film critics. He also became known internationally for starring in many British films such as My Son the Fanatic (1997), East is East (1999) and The Parole Officer (2001). As well as these he appeared in Hollywood films including City of Joy (1992), opposite Patrick Swayze; Wolf (1994) alongside Jack Nicholson and The Ghost and the Darkness (1996) opposite Val Kilmer. In 2007, he appeared as General Zia-Ul-Haq in Charlie Wilson's War, which stars Tom Hanks and Julia Roberts.

He has also worked in Hindi television serials like Kakkaji Kaheen (1988) (roughly meaning Uncle says) as a paan-chewing Kakkaji, which was a parody on politicians and Mr. Yogi (1989) as a suave Sutradhaar who enjoys pulling the protagonist's leg. These two serials underlined Om Puri's versatility as a comedian. He received critical acclaim for him performance in Govind Nihalani's television film Tamas (1987) based on a Hindi novel of the same name. He also essayed comic roles in Hindi films like Jaane Bhi Do Yaaron which reached a cult status, followed by Chachi 420 (1997), Hera Pheri (2000), Chor Machaye Shor (2002) and Malamaal Weekly (2006).

His more recent Hindi film roles include Singh Is Kinng, Mere Baap Pehle Aap and Billu. Puri was seen in the role of Mohammad Ali Kasuri in Road to Sangam (2009). In 2010, he appeared in The Hangman.