Khan is the eldest son of celebrated a screenwriter Salim Khan who has to his credit several successful films like Sholay, Deewar and Don, and his first wife Salma Khan (maiden name Sushila Charak). His stepmother is Helen, a famous yesteryear Bollywood actress, who has co-starred with him in Khamoshi: The Musical (1996) and Hum Dil De Chuke Sanam (1999). He has two brothers, Arbaaz Khan and Sohail Khan, and two sisters, Alvira and Arpita. Alvira is married to actor/director Atul Agnihotri.

Khan is a dedicated bodybuilder. He trains everyday and is famous for taking off his shirt in movies and stage shows alike. In 2004, he was voted 7th best-looking man in the World and the best looking man in India by People magazine, U.S. Khan has been involved in several charities during his career.

Despite being romantically linked with several actresses, and having relationships with ex-girlfriends Aishwarya Rai, Somy Ali and Sangeeta Bijlani, Khan is frequently featured by Indian media as Bollywood's most eligible bachelor. He has been dating model-turned-actress Katrina Kaif since 2003.

On 11 October 2007, Khan accepted an offer from Madame Tussauds wax museum in London to have a wax replica made of himself. His life-size wax figure was finally installed there on 15 January 2008, making him the fourth Indian actor to have been replicated as a wax statue in the museum.