In December 1637, an alliance of local rōnin and mostly Catholic peasants led by Amakusa Shirō rebelled against the Tokugawa shogunate due to discontent over Katsuie's policies.

The Tokugawa shogunate sent a force of over 125,000 troops supported by the Dutch to suppress the rebels, which defeated them after a lengthy siege against their stronghold at Hara Castle in Minamishimabara.

Following the successful suppression of the rebellion, Shirō and an estimated 37,000 rebels and sympathizers were beheaded, and the Portuguese traders suspected of helping them were expelled from Japan.

The inhabitants of the Amakusa Islands, which had been part of the fief of Konishi Yukinaga, suffered the same sort of persecution at the hands of the Terasawa family, which, like the Matsukura, had been granted the territory.

[9] Another growing problem was the presence of numerous unemployed samurai, including former retainers of Katō Tadahiro and Sassa Narimasa, both of whom had once ruled parts of Higo Province.

At this point they gathered near the ruins of Hara Castle, which had been the home of the Arima clan before their move to the Nobeoka Domain and was subsequently demolished.

[12] They built up palisades using the wood from the boats they had crossed the water with, and were greatly aided in their preparations by the weapons, ammunition, and provisions they had plundered from the Matsukura clan's storehouses.

[15] Nicolaes Couckebacker, Opperhoofd of the Dutch factory (trading post) on Hirado oversaw the transfer of military stores, and when the shogunate forces requested naval support, he personally accompanied the vessel de Ryp to a position offshore, near Hara Castle.

[16] The ship withdrew at the request of the Japanese, following contemptuous messages sent by the rebels to the besieging troops: Are there no longer courageous soldiers in the realm to do combat with us, and weren't they ashamed to have called in the assistance of foreigners against our small contingent?

[18] However, the rebels at Hara Castle, who were led by well-trained former samurai, resisted the siege for months and caused the shogunate heavy losses.

[citation needed] On 12 April 1638, troops under the command of the Kuroda clan of Hizen stormed the fortress and captured the outer defenses.

[21] The Shimabara rebellion was the first massive military effort since the Siege of Osaka where the shogunate had to supervise an allied army made up of troops from various domains.

Amakusa Shirō's severed head was taken to Nagasaki for public display, and the entire complex at Hara Castle was burned to the ground and buried, together with the bodies of all the dead.

[24] Another part of the shogunate's actions after the rebellion was to excuse the clans which had aided its efforts militarily from the building contributions which it routinely required from various domains.

Towns on the Shimabara peninsula also continue to have a varied mix of dialects due to the mass immigration from other parts of Japan.

[citation needed] With the exception of periodic, localized peasant uprisings, the Shimabara Rebellion was the last large-scale armed clash in Japan until the Boshin War.