Puri's first film was Chor Chor Chhup ja, a children's film.
During this time, to make ends meet he also worked at the Actors' Studio, where future actors such as Gulshan Grover and Anil Kapoor would be his students.

Subsequently, Puri worked in numerous Indian films, as well as many films produced in the United Kingdom and the United States.

Puri made his debut in the mainstream films genre in the 1976 Marathi film Ghashiram Kotwal, based on a Marathi play of the same name by Vijay Tendulkar.
It was directed by K. Hariharan and Mani Kaul in cooperation with 16 graduates of the FTII.
He has claimed that he was paid "peanuts" for his best work.
Along with Amrish Puri, Naseeruddin Shah, Shabana Azmi and Smita Patil, he was among the main actors who starred in what was then referred to as art films such as Bhavni Bhavai (1980), Sadgati (1981), Ardh Satya (1982), Mirch Masala (1986) and Dharavi (1992).

He was critically acclaimed for his performances in many unconventional roles such as a victimized tribal in Aakrosh (1980); Jimmy's manager in Disco Dancer (1982); a police inspector in Ardh Satya (1982), for which he got the National Film Award for Best Actor; a humble husband in Seepeeyan (1984), Vinod's uncle in Zamana (1985 film) the leader of a cell of Sikh militants in Maachis (1996); as a tough cop again in the commercial film Gupt in 1997; and as the courageous father of a martyred soldier in Dhoop (2003).

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

Puri had a cameo in the highly acclaimed film Gandhi (1982, directed by Richard Attenborough).
In the mid-1990s, he diversified to play character roles in mainstream Hindi cinema, where his roles are more tuned to mass audiences than film critics.
He became known internationally by starring in many British films such as My Son the Fanatic (1997), East Is East (1999) and The Parole Officer (2001).
He appeared in Hollywood films including City of Joy (1992), opposite Patrick Swayze; Wolf (1994) with 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 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 his performance in Govind Nihalani's television film Tamas (1988) based on a Hindi novel of the same name.
He played comic roles in Hindi films like Jaane Bhi Do Yaaro which reached a cult status, followed by Chachi 420 (1997), Hera Pheri (2000), Chor Machaye Shor (2002), Deewane Hue Pagal, Chup Chup Ke, Kismet Connection and Malamaal Weekly (2006) and Oh My God.
He was regular in films directed by Priyadarshan and Kamal Haasan.

His notable roles in commercial Hindi films included Drohkaal, In Custody, Narsimha, Ghayal, Mrityudand, Aastha, Hey Ram, Pyar Toh Hona Hi Tha, Farz, Gadar, Lakshya,  Dev (2004), Rang De Basanti,  Yuva, Singh Is Kinng, Mere Baap Pehle Aap, Billu, Kyunki, Lakshya, Dabang, Bhaji In Problem, Khap, Bajrangi Bhaijaan, Ghayal Once Again.
Puri was seen in the role of Mohammad Ali Kasuri in Road to Sangam (2009).
In 2010, he appeared in The Hangman.
In 2011 he was in the Indian action film Don 2.

He has also worked in some episodes of the TV series Aahat during the second season which was aired between 2004 and 2005 on Sony channel.
Other notable television appearances included Bharat Ek Khoj, Yatra, Mr. Yogi,
Puri's first film was Chor Chor Chhup ja, a children's film. During this time, to make ends meet he also worked at the Actors' Studio, where future actors such as Gulshan Grover and Anil Kapoor would be his students.
Subsequently, Puri worked in numerous Indian films, as well as many films produced in the United Kingdom and the United States.
Puri made his debut in the mainstream films genre in the 1976 Marathi film Ghashiram Kotwal, based on a Marathi play of the same name by Vijay Tendulkar. It was directed by K. Hariharan and Mani Kaul in cooperation with 16 graduates of the FTII. He has claimed that he was paid "peanuts" for his best work. Along with Amrish Puri, Naseeruddin Shah, Shabana Azmi and Smita Patil, he was among the main actors who starred in what was then referred to as art films such as Bhavni Bhavai (1980), Sadgati (1981), Ardh Satya (1982), Mirch Masala (1986) and Dharavi (1992).
He was critically acclaimed for his performances in many unconventional roles such as a victimized tribal in Aakrosh (1980); Jimmy's manager in Disco Dancer (1982); a police inspector in Ardh Satya (1982), for which he got the National Film Award for Best Actor; a humble husband in Seepeeyan (1984), Vinod's uncle in Zamana (1985 film) the leader of a cell of Sikh militants in Maachis (1996); as a tough cop again in the commercial film Gupt in 1997; and as the courageous father of a martyred soldier in Dhoop (2003).
In 1999, Puri acted in a Kannada film A.K. 47 as a strict police officer who tries to keep the city safe from the underworld—it became a huge commercial hit. Puri's acting in the film is memorable. He rendered his own voice for the Kannada dialogues. In the same year, he starred in the successful British comedy-drama film East is East, where he played a first-generation Pakistani immigrant in Northern England, struggling to come to terms with his far more westernised children.
Puri had a cameo in the highly acclaimed film Gandhi (1982, directed by Richard Attenborough). In the mid-1990s, he diversified to play character roles in mainstream Hindi cinema, where his roles are more tuned to mass audiences than film critics. He became known internationally by starring in many British films such as My Son the Fanatic (1997), East Is East (1999) and The Parole Officer (2001). He appeared in Hollywood films including City of Joy (1992), opposite Patrick Swayze; Wolf (1994) with 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 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 his performance in Govind Nihalani's television film Tamas (1988) based on a Hindi novel of the same name. He played comic roles in Hindi films like Jaane Bhi Do Yaaro which reached a cult status, followed by Chachi 420 (1997), Hera Pheri (2000), Chor Machaye Shor (2002), Deewane Hue Pagal, Chup Chup Ke, Kismet Connection and Malamaal Weekly (2006) and Oh My God. He was regular in films directed by Priyadarshan and Kamal Haasan.
His notable roles in commercial Hindi films included Drohkaal, In Custody, Narsimha, Ghayal, Mrityudand, Aastha, Hey Ram, Pyar Toh Hona Hi Tha, Farz, Gadar, Lakshya,  Dev (2004), Rang De Basanti,  Yuva, Singh Is Kinng, Mere Baap Pehle Aap, Billu, Kyunki, Lakshya, Dabang, Bhaji In Problem, Khap, Bajrangi Bhaijaan, Ghayal Once Again. Puri was seen in the role of Mohammad Ali Kasuri in Road to Sangam (2009). In 2010, he appeared in The Hangman. In 2011 he was in the Indian action film Don 2.
He has also worked in some episodes of the TV series Aahat during the second season which was aired between 2004 and 2005 on Sony channel. Other notable television appearances included Bharat Ek Khoj, Yatra, Mr. Yogi, 
Om Puri