Perlman was born in Tel Aviv which, three years later, became part of the state of Israel. When he was small he listened to the violin on the radio and decided he wanted to play it. He studied at the Academy of Music in Tel Aviv. Then he moved to the United States to study at the Juilliard School with Ivan Galamian and Dorothy DeLay. He made his debut (first public performance) at Carnegie Hall in 1963. In 1964 he won the Leventritt Competition. Soon afterward he began to tour widely. He also appeared on American television in shows including Sesame Street. He was invited to play at the White House.
Perlman had been ill with polio at the age of four. He got better, and managed to learn to walk again with the use of crutches. Today, he still walks with crutches and plays the violin sitting down.
In 1987, he joined the Israel Philharmonic Orchestra for their concerts in Warsaw and Budapest, as well as other Eastern bloc countries. He toured with the IPO in the spring of 1990 for their first-ever performance in the USSR, with concerts in Moscow and Leningrad, and toured with the IPO again in 1994, performing in China and India.
Perlman usually plays classical music but sometimes he plays jazz. He made an album made with jazz pianist Oscar Peterson, and klezmer. Perlman has been a soloist for a number of movie scores, including the score of the 1993 film Schindler's List by John Williams.
Perlman has made many recordings and received many great honours.
Perlman performed at Barack Obama's presidential inauguration. He joined cellist Yo-Yo Ma, pianist Gabriela Montero and clarinetist Anthony McGill. Together they played "Air and Simple Gifts" a new arrangement by John Williams based on the Shaker hymn "'Tis A Gift To Be Simple." 
Itzhak Perlman lives in New York City with his wife. They have five children.