As a performer, Vilayat Khan is the sixth generation of a renowned family of sitarists. Vilayat Khan's great grandfather Ustad Sahabdat Khan gave the Surbahar (Bass Sitar) the final form that it has today. His grandfather, Ustad Imdad Khan, pioneered the Imdad Khani Gharana (tradition) of sitar technique. In this tradition, Ustad Imdad Khan brought human vocal profundity to the sitar, drawing upon khyal (Indian vocal technique). Vilayat Khan's father and teacher, Ustad Inayat Khan, continued and expanded this traditon. Vilayat Khan has continued and expanded it as well. He has introduced his own innovations in sitar performance, including the 'gayaki' ang style of vocalization.

By the age of four, Vilayat Khan was playing the sitar. At eight, his first public performance catapulted him to fame. Since then, Vilayat Khan has performed throughout India, the United States and Europe, including concerts at Buckingham Palace, the enormous Royal Albert Hall, and the royal courts of Iran and Afghanistan. Often loudspeakers have had to be placed outside packed auditoriums to make his music available to disappointed fans who were turned away due to lack of seating.

Vilayat Khan has extensively recorded the traditional classical music of India and his own compositions within that tradition. Such compositions include his film scores, including scores for films by Satyajit Ray and by Merchant and Ivory.

Vilayat Khan is called "Aftaab-e-Sitar", the radiant star of the sitar, a title conferred on him by the late President of India, Fakhruddin Ali Ahmed. Revered guitar genius Andres Segovia called Vilayat Khan "a genius one of the handful of the world's greatest musicians." The San Francisco Chronicle and Le Monde of Paris both called him "The greatest sitarist of the century."