Nulato lies on the west bank of the Yukon River, across the river from the Innoko National Wildlife Refuge.
Nulato served as the trading site between Athabascans and Inupiat Eskimos from the Kobuk area. Western contact increased rapidly after the 1830s - a Russian trading post was established here in 1839. Nulato became the center for missionary activity, and many area Natives moved to the village after a Roman Catholic school and mission were completed in the late 1800s. Food shortages and a measles epidemic combined to kill one-third of the Nulato population during 1900.
The city was incorporated in 1963. A large-scale housing development began at a new townsite on the hills 2 miles north Nulato. Trapping is a major income source for Nulato residents.