Perlman was born in Tel Aviv. He contracted polio at the age of four, leaving him on crutches, and meaning he has to play the violin seated even today. He studied at the Academy of Music there. He moved to the United States to study at the Juilliard School, and made his debut at Carnegie Hall in 1963.
Soon, Perlman began to tour extensively. He has made a large number of records, and from the 1970s began to appear on shows such as The Tonight Show and Sesame Street, as well as playing at a number of functions at the White House.
As well as playing and recording the classical music for which he is best known, Perlman has also played jazz and klezmer. Recently, he has also begun to conduct, taking the post of Principal Guest Conductor at the Detroit Symphony Orchestra.
Perlman has received many honors, including Kennedy Center Honors in 2003.