Karl Barry Sharpless (born April 28, 1941) is a chemist renowned for his work on organometallic chemistry.

In 2001 he won the Nobel Prize in Chemistry for his work on stereoselective oxidation reactions (Sharpless epoxidation, Sharpless bishydroxylation). This prize was shared with William S. Knowles and Ryoji Noyori (for their work on stereoselective hydrogenation). Currently he spends much of his time promoting "click" reactions which are selective, exothermic reactions which occur under mild conditions in water; the most successful variant of which is the alkyne-azide [2 + 3] cycloaddition.

Sharpless was born in Philadelphia. He began his studies in Dartmouth College and earned his PhD from Stanford University in 1963. He continued post-doctoral work at Stanford University and Harvard University.

Sharpless became professor at the Massachusetts Institute of Technology, Stanford University, and the Scripps Research Institute, where currently holds the W. M. Keck professorship in chemistry.

An interesting personal note, as passed around by graduate students at Scripps Research Institute: Barry is notorious for eating/tasting chemicals that he finds on his students' benches. In fact, he once ate osmium tetroxide while giving a seminar. Osmium tetroxide, while incredibly useful in organic synthesis, has a high vapor pressure and will permanently blind you if the vapors get in your eye. Barry also has only one eye; the other was injured when, as a graduate student, an NMR tube exploded in his face. He is a lab safety advocate at TSRI.

Sharpless is known for asking very long questions at seminars. The seminar might be about transition metal spectroscopy, and he will start a question with, "I had an ear infection once..." This amuses graduate students to no end. On no less than three occasions, he has referenced the act of urination during Q&A sessions after seminars given by distinguished speakers.