William Leo Nyhan (born March 13, 1926) is an American physician best known as the co-discoverer of Lesch–Nyhan syndrome.

He has held positions at Johns Hopkins School of Medicine and the Miller School of Medicine at the University of Miami, and has served on a number of advisory committees, pediatric advisory boards, and research foundation boards.

He has studied the neuropathology of propionic acidemia, including the manifestation of basal ganglia infarction and its neurologic, non-metabolic presentation.

He is involved in the ongoing development of tandem mass spectrometry for use in newborn screening and research.

In addition, he is investigating the use of dichloroacetate to treat a broad range of mitochondrial diseases that lead to lactic acidemia.