Karl Barry Sharpless (born April 28, 1941) is an American stereochemist. He is a two-time Nobel laureate in Chemistry known for his work on stereoselective reactions and click chemistry.
Sharpless was awarded half of the 2001 Nobel Prize in Chemistry "for his work on chirally catalysed oxidation reactions", and one third of the 2022 prize, jointly with Carolyn R. Bertozzi and Morten P. Meldal, "for the development of click chemistry and bioorthogonal chemistry". Sharpless is the fifth person (in addition to two organizations), to have twice been awarded a Nobel prize, along with Marie Curie, John Bardeen, Linus Pauling and Frederick Sanger, and the third to have been awarded two prizes in the same discipline (after Bardeen and Sanger).