Perlman was born in 1945 in Tel Aviv. His parents, Chaim and Shoshana Perlman, were Jewish natives of Poland and had independently immigrated to the British Mandate of Palestine (now Israel) in the mid-1930s before they met and later married. Perlman contracted polio at age four and has walked using leg braces and crutches since then and plays the violin while seated. As of 2018, he uses crutches or an electric Amigo scooter for mobility.

Perlman appeared on The Ed Sullivan Show twice in 1958, and again in 1964, on the same show with the Rolling Stones. He made his debut at Carnegie Hall in 1963 and won the Leventritt Competition in 1964. Soon afterward, he began to tour widely. In addition to an extensive recording and performance career, he has continued to make guest appearances on American television shows such as The Tonight Show and Sesame Street as well as playing at a number of functions at the White House.

In 1975, Perlman accepted a faculty post at the Conservatory of Music at Brooklyn College. In 2003, Mr. Perlman was named the holder of the Dorothy Richard Starling Foundation Chair in Violin Studies at the Juilliard School, succeeding his teacher, Dorothy DeLay. He also currently teaches students one-on-one at the Perlman Music Program on Long Island, NY, rarely holding master classes.

Although he has never been billed or marketed as a singer, he sang the role of “Un carceriere” (“a jailer”) on a 1981 EMI recording of Puccini’s “Tosca” that featured Renata Scotto, Plácido Domingo, and Renato Bruson, with James Levine conducting. He had earlier sung the role in an excerpt from the opera on a 1980 Pension Fund Benefit Concert telecast as part of the Live from Lincoln Center series with Luciano Pavarotti as Cavaradossi and Zubin Mehta conducting the New York Philharmonic.

On 5 July 1986, he performed on the New York Philharmonic’s tribute to the 100th anniversary of the Statue of Liberty, which was televised live on ABC Television in the United States. The orchestra, conducted by Zubin Mehta, performed in Central Park.

In 1987, he joined the Israel Philharmonic Orchestra (IPO) for their concerts in Warsaw and Budapest as well as other cities in Eastern bloc countries. He toured with the IPO in the spring of 1990 for its first-ever performance in the Soviet Union, with concerts in Moscow and Leningrad, and toured with the IPO again in 1994, performing in China and India.

While primarily a solo artist, Perlman has performed with a number of other musicians, including Yo-Yo Ma, Pinchas Zukerman, Jessye Norman, Isaac Stern, and Yuri Temirkanov at the 150th anniversary celebration of Tchaikovsky in Leningrad in December 1990. He has also performed and recorded with his friend and fellow Israeli violinist/violist Pinchas Zukerman on numerous occasions over the years.

The Perlman Music Program, founded in 1994 by Perlman’s wife, Toby Perlman, and Suki Sandler, started as a summer camp for exceptional string musicians between the ages of 12 and 18. Over time, it expanded to a year-long program. Students have the chance to have Itzhak Perlman himself coach them before they play at venues such as the Sutton Place Synagogue and public schools. By introducing students to each other and requiring them to practice together, the program strives to have musicians who would otherwise practice alone and develop a network of friends and colleagues. Rather than remain isolated, participants in the program find an area where they belong.

Perlman played at the state dinner attended by Queen Elizabeth II on 7 May 2007, in the East Room at the White House.

At the beginning of the new millennium, Perlman began to conduct. He took the post of principal guest conductor at the Detroit Symphony Orchestra. He served as music advisor to the Saint Louis Symphony Orchestra from 2002 to 2004. In November 2007, the Westchester Philharmonic announced the appointment of Perlman as artistic director and principal conductor. His first concert in these roles was on 11 October 2008, in an all-Beethoven program featuring pianist Leon Fleisher performing the Emperor Concerto.

In 2015 on a classical music program entitled The Chamber Music Society of Lincoln Center produced by WQXR in New York City, it was revealed that Perlman performed the uncredited violin solo on the 1989 Billy Joel song “The Downeaster Alexa”.

On 2 November 2018, Perlman reprised the 60th anniversary of his first appearance on The Ed Sullivan Show as a guest on The Late Show with Stephen Colbert.