However, as an adult when he moved to Mumbai, Puri looked up when Dussehra was celebrated in 1950, to establish his birth date as 18 October.

[16] A fellow NSD student who became a long-term friend, Naseeruddin Shah, encouraged Puri to follow him to the Film and Television Institute of India in Poona (present-day Pune).

[15][17] In an interview with The Times of India, Puri later recounted his family was so poor that he did not have a decent shirt to wear when he joined FTII.

[23] 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);[24] Jimmy's manager in Disco Dancer (1982);[25] a police inspector in Ardh Satya (1982),[25] for which he got the National Film Award for Best Actor;[26] a humble husband in Seepeeyan (1984),[27] Vinod's uncle in Zamana 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).

[28] In 2007, he appeared as General Zia-ul-Haq in Charlie Wilson's War, which stars Tom Hanks and Julia Roberts.

[27] 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.

He received critical acclaim for his performance in Govind Nihalani's television film Tamas (1988)[25] 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,[27] 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.

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, Dabangg, Bhaji in Problem, Khap, Bajrangi Bhaijaan, Ghayal Once Again.

Other notable television appearances included Bharat Ek Khoj, Yatra, Mr. Yogi, Kakaji Kahin, Sea Hawks, Antaral and Savdhaan India's second season.

[37] In an interview to Rajya Sabha TV in 2012, Om Puri spoke about his interest in agriculture and cooking, and suggested that his dream was to open a dhaba by the name Daal Roti.

[38] In October 2016, Puri appeared for a debate on a news channel regarding a Hindi film producer's ban on Pakistani actors after the Uri attack.

During the debate, he made insulting comments about Indian soldiers which led to heavy criticism on social media.