Knopfler was originally best-known as the lead guitarist and vocalist for the English rock band, Dire Straits, which he co-founded in 1977 with his brother David. Following the dissolution of Dire Straits in 1995, Knopfler has continued to record and produce albums as a solo artist, under his own name. Occasionally, Knopfler has played in other groups, such as the "supergroup" The Notting Hillbillies, and has guested on works by other artists, including Bob Dylan, Bryan Ferry, Eric Clapton, John Fogerty, Jools Holland, Steely Dan and Chet Atkins. He has produced albums for artists such as Tina Turner, Randy Newman, Bob Dylan and Emmylou Harris. In addition, he has scored the music to several films, including Local Hero, Cal, Last Exit to Brooklyn, Wag the Dog, and Rob Reiner's classic, The Princess Bride.

He is one of the most respected fingerstyle guitarists of the modern rock era. Knopfler was ranked #27 on Rolling Stone magazine's list of "100 Greatest Guitarists of All Time".