Karl Barry Sharpless (born 28 April 1941) is an American chemist known for his work on stereoselective reactions. In 2001 he won a half-share of the Nobel Prize in Chemistry for his work on stereoselective oxidation reactions (Sharpless epoxidation, Sharpless asymmetric dihydroxylation, Sharpless oxyamination). The other half of the year's Prize was shared between William S. Knowles and Ryōji Noyori (for their work on stereoselective hydrogenation).

He earned his Ph.D from Stanford University in 1968. He holds honorary degree of Technical University of Munich. He also successfully epoxidized (using racemic tartaric acid) a C-86 Buckminster Fullerene ball, employing p-Cresol as solvent.