During the 16th century, Catholic missionaries and traders from Portugal arrived and became active in Hirado and Nagasaki, which became a major center for foreign trade.

After being given free rein in Oda Nobunaga's period, the missionaries were forced out little by little, until finally, in the Tokugawa era, Christianity was banned under the Sakoku national isolation policy: Japanese foreign trade was restricted to Chinese and Dutch traders based at Dejima in Nagasaki.

The majority was sent to Jagatara (Jakarta) and are still remembered by the locals as the people who wrote the poignant letters which were smuggled across the sea to their homeland.

On August 9, 1945, the United States dropped an atomic bomb on Nagasaki, which destroyed all buildings in a 1.6 kilometres (1.0 mi) radius from the point of impact and extensively damaged other parts of the city.

In July 1957, mainly in the Isahaya area, damage from heavy rains, flooding and landslides lead to a death toll of 586, with 136 people missing and 3,860 injured.

Most of the prefecture is near the coast and there are a number of ports such as Nagasaki and a United States Navy base at Sasebo.

[3] Thirteen cities are located in Nagasaki Prefecture: These are the towns and villages of each district: The following municipalities have been dissolved since the year 2000.

The current governor of Nagasaki is Kengo Oishi, who defeated three-term incumbent Hōdō Nakamura in 2022.