He is known for his studies into the etiology of yellow fever and malaria, including the theory that they are caused by germs, and for his espousal of scientific racism.

[2] Nott took up the theory that malaria and yellow fever were caused by parasitic infections with "animalcules" (microorganisms), earlier held by John Crawford.

[6] Citing Nott's need, Kentucky Senator Joseph R. Underwood had the racial category of "mulatto" added to the 1850 United States Census.

According to Nott, the monuments and artifacts found in Egypt show us that the "White, Mongolian and Negro existed at least five thousand years ago."

According to Nott, there are no verses in the Bible that support monogenism and that the only passage used by the monogenists Acts 17:26, "And [he] hath made of one blood all nations of men for to dwell on all the face of the earth, and hath determined the times before appointed, and the bounds of their habitation;"[10] was interpreted by them wrongly since the "one blood" of Paul's sermon included only the nations that he knew existed, which were local.

Charles Darwin opposed Nott and Gliddon's polygenist and creationist arguments in his 1871 The Descent of Man, arguing for a monogenism of the human species.

It attracted controversy in 2016, with several student groups petitioning the building to be renamed or an educational plaque to be added because of Nott's open racism even by the standards of his era.

[17] While originally believing that the Egyptians were purely Caucasian, the authors of Types of Mankind (1854) modified their views based on excavations from earlier dynasties.

"[19] Specifically, in 1854, Josiah Nott and George R. Gliddon noted that according to majority of ethnographers and Samuel George Morton's own anthropological works, "the Fellahs of Upper and Middle Egypt, at the present day, continue to be an unmistakable race, and are regarded by most travelled authorities as the best living representatives of the ancient population of Egypt."

They would also take the position that, "the iconographic monuments of the IVth, Vth, and VIth dynasties, is closely analogous to the predominant type of that day; which fact serves to strengthen our view that the Egyptians of the early dynasties were rather of an African or Negroid type-resembling the Bishari in some respects, and in others the modern Fellah, or peasantry of Upper Egypt.

[21] From the 1911 Encyclopedia Britannica "It is most convenient, however, to refer to the dark-skinned inhabitants of this zone by the collective term of Negroids, and to reserve the word Negro for the tribes which are considered to exhibit in the highest degree the characteristics taken as typical of the variety.

"[22] Samuel Morton addressed several letters to George Gliddon and stated that he modified many of his old views on ancient Egypt, believing their origins to be similar to Barabra populations, but not Negroes.