Irfan Khan was born in Jaipur to a Muslim Nawab family. Khan's mother is Sayeeda Begum from Tonk Hakim Family and his father was the late Jagirdar of Khajuriya village near Tonk Dist. He was studying for his M.A. degree when he earned a scholarship to study at National School of Drama (NSD) in New Delhi in 1984.

Khan is married to writer Sutapa Sikdar who's also a NSD graduate and they have two children named Babil and Ayan. He has two brothers, Imran Khan and Salman Khan and one sister Rukhsana Begum. They still live in Jaipur and run their businesses.

After graduating in 1987, Khan moved to Mumbai, where he acted in television serials like Chanakya, Sara Jahan Hamara, Banegi Apni Baat, Chandrakanta , Star Bestsellers for Star Plus, and Sparsh. He was the main villain in a series called Darr which aired on Star Plus, where he played the role of a psycho serial killer, opposite Kay Kay Menon. He also played the role of famous revolutionary Urdu poet and Marxist political activist of India Makhdoom Mohiuddin in Kahkashan produced by Ali Sardar Jafri.

He also appeared in a serial called Bhanvar aired on SET India. Mira Nair offered him a cameo in Salaam Bombay (1988) though his role was edited out in the final film.

In the 1990s he appeared in the critically acclaimed film Ek Doctor Ki Maut and Such a Long Journey 1998 and various other films which went unnoticed.

After many unsuccessful films, things changed when London-based director Asif Kapadia gave him the lead in The Warrior, a historical film completed in 11 weeks on location in Himachal Pradesh and Rajasthan. In 2001 The Warrior opened in international film festivals, making Irrfan Khan a known face.

In 2003 he acted in Indian born writer-director, Asvin Kumar's short film, Road to Ladakh. That same year he played the title role in the critically acclaimed Maqbool, an adaptation of Shakespeare's Macbeth.

His first Bollywood main lead role came in 2005 with film Rog. In 2004 he won the Filmfare Best Villain Award for his role in film Haasil.

In 2007, he appeared in the box office hits Metro, for which he received a Filmfare Best Supporting Actor Award, and The Namesake. Also his appearance in the international films A Mighty Heart and The Darjeeling Limited.

He anchored a show Mano Ya Na Mano airing on Star One. He hosted another programme named Kyaa Kahein which was similar to Mano Ya Na Mano.

He played the police inspector in the 2008 film Slumdog Millionaire.
He Acted in the movie Acid Factory. He also appeared as an FBI agent in New York, and a Police Inspector in Right Yaaa Wrong.

Irfan Khan's forthcoming film are Paan Singh Tomar, Bhopal, Thank You.