Nichols was born as son of John White Treadwell Nichols in Jamaica Plain, Boston, Massachusetts. In 1906 he studied vertebrate zoology at Harvard College where he graduated to Bachelor of Arts (AB). In 1907 he joined the American Museum of Natural History as assistant in the department of mammalogy. In 1913 he founded Copeia the official journal of the American Society of Ichthyologists and Herpetologists. In 1916 he described the long lost Bermuda Petrel together with Louis Leon Arthur Mowbray who first sighted this bird within a flock of other petrels in 1906 on Castle Island, Bermuda 45 years before it was officially rediscovered by Mowbray's son Louis. He also described the fish genus Bajacalifornia. He also worked with a team of scientists from the American Museum of Natural History during the Jersey Shore shark attacks of 1916. From 1913 to 1952 he was first assistant curator, then associate curator in charge and finally curator in the Department of Ichthyology at the American Museum of Natural History.
Nichols wrote 1,000 articles and several books (mostly about fish but also about birds) and he made many expeditions around the world.