Simon Keenlyside was born in London, and studied zoology at Cambridge, and singing with John Cameron at the Royal Northern College of Music in Manchester.

He made his operatic début at the Hamburg State Opera as Count Almaviva in Le nozze di Figaro. He has since appeared in leading rôles in major opera houses throughout Europe and in the United States, including La Scala, Milan, the Paris Opéra, Covent Garden and the Metropolitan Opera in New York.

He enjoys extensive concert work, appearing with the Chamber Orchestra of Europe and the Berlin Philharmonic under Abbado, the City of Birmingham Symphony under Rattle, the London Symphony Orchestra under Colin Davis, the Philharmonia under Dohnányi and Sawallisch, the Cleveland Orchestra under Welser-Möst, the Vienna Philharmonic under Muti and the Czech Philharmonic Orchestra under Charles Mackerras.

He has appeared in recital in New York, San Francisco, Lisbon, Geneva, Moscow, Paris, Amsterdam, Ferrara, Rome, Brussels, London, Graz, the Edinburgh Festival, Salzburg and Schubertiade Festivals, at La Scala Milan and both the Konzerthaus and Musikverein in Vienna.

His recordings include lieder and the title rôles in Don Giovanni and Billy Budd.