He made his debut in 1966 with Aakhri Khat. Through his career he appeared in more than 168 feature films and 12 short films. He received the Filmfare Best Actor Award three times and the BFJA Awards for Best Actor (Hindi) four times. In 1991, he was awarded the Filmfare Special Award and in 2005, he received the Filmfare Lifetime Achievement Award. He was the highest paid Indian actor from 1970 to 1987 where Amitabh Bachchan shared the same tag with Khanna from 1980 to 1987.
He was also a Lok Sabha member of the Indian National Congress from New Delhi (Lok Sabha constituency) from 1992 to 1996.
He married Dimple Kapadia in March 1973, eight months before her debut film Bobby was released and had two daughters from the marriage. Their elder daughter Twinkle Khanna is married to actor Akshay Kumar, while they also have a younger daughter Rinke Khanna.
After being critically ill, Khanna died on 18 July 2012. Khanna has been posthumously awarded India's third highest civilian honour Padma Bhushan. On 30 April 2013 he was officially bestowed with the title The First Superstar of Indian cinema at Dadasaheb Phalke Academy Awards He has also been honored with a stamp and statue of his likeness, and a road being renamed in his honor.