Khanna was born in a Punjabi Hindu family to Kamla and Krishanchand Khanna on 6 October 1946, in Peshawar, British India (now in Pakistan). He had three sisters and one brother. Shortly after his birth, India was partitioned and the family left Peshawar and moved to Bombay (present-day Mumbai).

He attended St. Mary’s School, Bombay until class II and then transferred to Delhi. In 1957, the family moved to Delhi where he attended Delhi Public School, Mathura Road. Although the family moved back to Bombay in 1960, he was sent to Barnes School in Deolali, near Nashik. During his time at the boarding school Khanna watched the epics Solva Saal and Mughal-e-Azam and fell in love with motion pictures. He graduated with a commerce degree from Sydenham College, Bombay. He loved cricket. “The public may think I am just another filmstar, but there was a time when I played fair cricket with (Test player) Budhi Kunderan. Later I played with Eknath Solkar at the Hindu Gym. I used to bat at No. 4 but settled for films the moment I realised I couldn’t be a Vishwanath! Even so cricket, not films, is my first love,” he wrote in The Illustrated Weekly of India in 1979.

Vinod was spotted by Sunil Dutt after graduation, and made his acting debut in Sunil Dutt’s 1968 film Man Ka Meet (directed by Adurthi Subba Rao) as a villain and in which Som Dutt was the hero, a remake of the Tamil film Kumari Penn. At the start of his career, he played supporting or villainous characters in films such as Purab Aur Paschim, Sachaa Jhutha, Aan Milo Sajna and Mastana in 1970, and in Mera Gaon Mera Desh, Mere Apne and Elaan in 1971.

Khanna met his first wife Gitanjali Taleyarkhan in college. Khanna married Gitanjali in 1971 and had two sons with her, Rahul and Akshaye; both became Bollywood actors. In 1975, he became a disciple of Osho and in the early 1980s, moved to Rajneeshpuram. Khanna and Gitanjali settled for a divorce in 1985.

From playing villain Khanna successfully switched over to playing the popular hero. He got his first break as the solo lead in Hum Tum Aur Woh (1971) opposite Bharathi Vishnuvardhan and followed it up with Gulzar’s Mere Apne. In 1973 his performance as an army officer facing death row in Gulzar’s Achanak, earned him critical acclaim. In 1974 he played a college professor in Imtihan, which proved successful even in the face of stiff competition from Roti Kapda Aur Makan and Majboor. Amar Akbar Anthony and Muqaddar Ka Sikandar in which he costarred Amitabh Bacchan went on to become the highest grossing Indian movies of 1977 and 1978 respectively. Muqaddar Ka Sikandar was the third highest-grossing Hindi movie in the 1970s after Sholay and Bobby. At the peak of his popularity he played a supporting role in the 1978 Main Tulsi Tere Aangan Ki a heroine-dominated movie with stalwarts Asha Parekh and Nutan.

Some of the successful movies of this era include Hatyara with Moushumi Chatterjee, Qaid with Leena Chandavarkar, Inkaar with Vidya Sinha, Aap Ki Khatir with Rekha, Khoon Ki Pukaar, Shaque and Adha Din Aadhi Raat with Shabana Azmi, and Daulat with Zeenat Aman. In 1980, he starred in Feroz Khan’s Qurbani (1980) which became the highest-grossing film of that year. He was, at the time, one of the highest paid actors in Hindi films.

Khanna became a follower of the spiritual teacher Osho (Rajneesh) and left the film industry in 1982.

In 1987, Khanna returned to films with Insaaf in which he costarred with Dimple Kapadia.

In 1990, upon returning to India, Khanna married Kavita Daftary, daughter of industrialist Sharayu Daftary. They had a son, Sakshi (born 1991), and a daughter, Shraddha.

In 1997, he launched his son Akshaye Khanna in Himalay Putra in which he also starred alongside him. In 1999, Vinod Khanna received a Filmfare Lifetime Achievement Award for his contribution to the industry for over three decades. Since then, he started playing character roles in films such as Deewaanapan (2002), Red Alert: The War Within, Wanted (2009), Dabangg (2010) and Dabangg 2(2012). In 2007, he starred in the Pakistani film Godfather.

In 1997, Khanna joined the Bharatiya Janata Party and was elected from Gurdaspur constituency in Punjab in the next year’s Lok Sabha poll. In 1999, he was re-elected to the Lok Sabha from the same constituency. Later, he became union minister for culture and tourism in July 2002. Six months later, he was moved to the Ministry of External Affairs (MEA) as Minister of State. In 2004 he won re-election from Gurdaspur. However, Khanna lost out in the 2009 general elections. In the 2014 general election he was again elected for the 16th Lok Sabha from the same constituency. No other Bollywood star has triumphed in four Lok Sabha polls (1998, 1999, 2004 and 2014). He also served as Union minister of state for tourism and culture, as well as external affairs.

Khanna also ventured into television, playing the male lead role of “Kashinath” in the Smriti Irani-produced Hindi serial mere apne, which aired on the channel 9X in 2009. In 2014, he played the lead role in Koyelaanchal, in which he played the role of a Godfather and leader of the coal mafia. His last film to be released before his death was the 2015 film Dilwale alongside Shah Rukh Khan. The film was directed by Rohit Shetty and released on 18 December 2015 worldwide. He also acted in the film Ek Thi Rani Aisi Bhi, a biopic based on the life and times of Vijaya Raje Scindia of Gwalior. The film was released on Zee TV. In 2020, a delayed film he had shot and completed in 2014 was released titled Guns of Banaras which officially marks his final film appearance.

Khanna was hospitalised at the Sir H.N. Reliance Foundation Hospital and Research Center in Girgaon, Mumbai on 2 April 2017 for a few weeks after suffering from severe dehydration. He died at 11:20 a.m. (IST) on 27 April, and it was revealed that he had been battling advanced bladder cancer. Although the news about his deteriorating health started to spread in early 2017, his family declined to disclose any information. He was cremated at the Worli Crematorium on the same day.