|His performance at Mira Nair's Salaam Bombay! (1988) was congratulated. He was noticed by the mainstream Hindi Cinema for his role as crime lord in Parinda (1989), for which he won his first National Best Supporting Actress Award and was awarded the Filmfare Best Supporting Actor Award. He became a director with his film Prahaar (1991), with Madhuri Dixit, for whom he trained for his role as an officer of the Indian army.
His role in Angaar (1992) earned him the Filmfare Best Villain Award. He co-starred with industry veteran Raaj Kumar in Tirangaa (1993). He played in Krantiveer (1994), a son of chance, in which he won the National Award for Best Actor and also won the Filmfare Award and the Star Screen Awards. Patekar portrayed a ghost in Abhay's children's film, which won two awards at the 42nd National Film Festival in 1994. He co-starred with Rishi Kapoor in Hum Dono (1995).
Patekar also played comic roles, as in Welcome (2007), in which he plays a powerful crime lord in Dubai, who once wanted to be an actor in the movies. He played in Sangeeth Sivan's film Ek (2009).
He played the role of a school principal in Paathshaala (2010). He also starred in Raajneeti (2010), a multi-star political film by Prakash Jha. In 2011, he starred in the critically acclaimed film Shagird and in a Marathi film Deool. His next film was Ram Gopal Verma's The Attacks of 26/11 (2013), based on the 2008 bombings in Mumbai, in which he played the role of Deputy Police Commissioner Rakesh Maria.
In 2014, he starred in another Marathi film Dr. Prakash Baba Amte - The Real Hero. In 2015, he made two sequels taking over his roles in Ab Tak Chhappan 2, a continuation of Ab Tak Chhappan and Welcome Back, a continuation of Welcome. In 2016, he played the role of Ganpatrao "Appa" Belwalkar in the film adaptation of Drama Natsamrat which had a great critical and commercial success. He played Shere Khan's voice in the Hindi version of The Jungle Book (2016).
Patekar is known for his simple lifestyle and his generosity by donating to charities. He has contributed financially to the reconstruction of flood-ravaged villages in Bihar through the charity Anubhuthi. All monetary compensation he obtained for his performance in the Paathshaala film was given by him to five different charities. When he received the Raj Kapoor Prize which carries a cash prize of Rs 10,00,000, he donated the entire amount for drought relief activities in Maharashtra.
He also provided financial support to farm families who committed suicide due to drought-induced debt. It distributed checks worth Rs 15,000 to 62 farm families in the Vidarbha area in August 2015 and 113 other families in Latour and Osmanabad districts of Marathwada in September 2015.