He began to learn acting from Acting Guru Sahitya Kalbhai Thakkar from 1960 to 1962. In 1962, he travelled to Bombay (Now Mumbai) and began to seek opportunities to act. In 1963, Hrishikesh Mukherjee advised him to learn acting professionally.
In 1964 Asrani joined the Film Institute in Poona (now Film and Television Institute of India, Pune) and finished his course in 1966. He impressed many others and made his acting break in 1967 with a Gujrati movie opposite budding actress Waheeda (Not legendary Waheeda Rahman but the Gujrati Actress). He acted in four other movies, mainly as Actor or supporting actor in Gujrati from 1967 to 1969 before landing his first Hindi movie role in Umang, a low budget movie, which also had Subhash Ghai and Paintal. In 1969, he was offered the role of Rajesh Khanna’s friend in Aradhana, but Rajesh was more comfortable with an older person and preferred Sujit Kumar. His old advisor, Hrishikesh Mukherjee also passed him over for the movie Anand, giving the role to an older person, but gave Asrani a role in Bawarchi. This role set the tone for a number of supporting or comic roles like Abhimaan (Supporting), Chala Murari Hero Banne (Comedy), Chupke Chupke (Comedy), Choti Si Baat (Comedy) or his most remembered role, as the Jailer in Sholay. He was hugely talked about in the 1970s and is one of Amitabh Bachchan’s close friends. In the 2007, Abhishek-Aishwarya Wedding, Asrani and Prem Chopra were the only two of Amitabh’s old friends invited.
In the 1980s, he acted in over 50 films but most of his roles were very minor mainly because the concept of a comedian was getting phased out and heroes preferred to do their own comedy. During this period in 1982, he set up a small Gujrati production company with fellow artistes Dinesh Hingoo, Harish Patel and Salim Parvez (son of famous supporting actor Yunus Parvez), the company dissolved in 1996 with a large profit. He also invested mainly in cloth and acted as investor for other actors, until 1991 when he lost a lot of money. From 1988 to 1993, he also was a Director for the Film Institute in Poona.
The 1990s and 2000s have also seen him in a number of blockbuster films like Jo Jeeta Wohi Sikander, Hera Pheri, Chup Chup Ke, Hulchul and Deewane Huye Pagal. He was an integral part of comedies by Sajid Nadiadwala or Priyadarshan, but his roles are very minor and he has a very short screen space.