He was born in Glasgow, Scotland, and moved with his family to Newcastle upon Tyne in the mid 1950s. He learned to play the guitar as a teenager, and after completing tertiary education and working for the Yorkshire Evening Post and then Loughton College, he became a full time musician in the 1970s. He is noted for being left-handed, but playing right-handed, and for fingerpicking instead of strumming or using a plectrum; fingerpicking is usually associated with the acoustic guitar, but Knopfler usually (but not always) plays an electric guitar, particularly the Fender Stratocaster.
Knopfler and his associated bands have sold over 100 million albums, and performed live to audiences totalling many millions. He has twin sons (Benji and Joseph), and a daughter Isabella; he holds a degree in English from Leeds University, and has been awarded an honorary music degree from Newcastle University.