The largest city in and capital of Nagasaki Prefecture, Nagasaki began as a small harbor town which quickly grew into a large port city following the accidental landing of Francis Xavier in nearby Kagoshima Prefecture and the establishment of trade with Portuguese merchants.

Nagasaki also became the point of entry of Christianity into Japan, and its daimyo, Oomura Sumitada, and many of its inhabitants converted to Christianity. However, Toyotomi Hideyoshi, wary of Christian influence in the region, ordered the expulsion of all missionaries 1587, an order that largely went unenforced. Although 26 Japanese and foreign Christians were executed in Nagasaki in 1597, Christianity was grudgingly tolerated until 1614, when Christianity was officially banned and all missionaries ordered to leave. Following the ban, the Tokugawa shogunate killed and tortured Christians across Japan to force them to renounce their faith.

The rebellion at Shimabara near Nagasaki in 1636-1638 convinced the government that Christianity and disloyalty were linked. 30,000 Japanese Christians were massacred and a policy of national isolation descended in 1639, closing foreign trader with all but the Dutch.

Isolationism only ended with the arrival of Commodore Perry's 'Black Ships' in 1853, and Nagasaki would become an important economic city once more after the Meiji Restoration. Its main industry was ship-building, a fact which made it a target for the second atomic bomb to be dropped on Japan during World War II.