Nachtwey started working as a newspaper photographer in 1976 at a small newspaper in New Mexico. In 1980, he moved to New York and began working as a freelance photographer. In 1981, Nachtwey covered his first overseas assignment in Northern Ireland illustrating civil strife. Nachtwey has documented a variety of armed conflicts and social issues. He spent considerable time in South Africa, Latin America, the Middle East, Russia, Eastern Europe, the former Soviet Union shooting pictures of war, conflict and famine, and images of socio-political issues (pollution, crime and punishment) in Western Europe and the United States. He currently lives in New York City.
Nachtwey has worked with TIME as a contract photographer since 1984. He worked for Black Star from 1980 until 1985 and was a member of Magnum Photos from 1986 until 2001. In 2001, he was a founding member of the VII Photo Agency.