Nesoryzomys darwini, also known as Darwin's nesoryzomys or Darwin's Galápagos mouse, is a species of rodent in the genus Nesoryzomys that lived on Santa Cruz Island in the Galápagos Islands. It was probably nocturnal and inhabited burrows or rock crevices under bushes. Only four specimens exist, collected by Frank Wonder between 12 and 16 January 1929. This extinction may have been caused by competition and disease created by the introduction of nonnative brown and black rats.
The other Nesoryzomys known from Santa Cruz, Nesoryzomys indefessus, is also extinct there; other species of the genus survive on different islands.