On the night of 21 May, two large earthquakes were followed by a collapse of the eastern flank of Mount Unzen's Mayuyama dome, causing a landslide which swept through the city of Shimabara and into Ariake Bay, triggering a great tsunami.

Towards the end of 1791, a series of earthquakes occurred on the western flank of Mount Unzen which gradually moved towards Fugen-dake (one of Mount Unzen's peaks).

In February 1792, Fugen-dake started to erupt, triggering a lava flow which continued for two months. Meanwhile, the earthquakes continued, shifting nearer to the city of Shimabara.

It is not known to this day whether the collapse occurred as a result of an eruption of the dome or as a result of the earthquakes. The tsunami struck Higo Province on the other side of Ariake Bay before bouncing back and hitting Shimabara again. Out of an estimated total of 15,000 fatalities, around 5,000 are thought to have been killed by the landslide, around 5,000 by the tsunami across the bay in Higo Province, and a further 5,000 by the tsunami returning to strike Shimabara. The waves reached a height of 33–66 ft (10–20 m), classing this tsunami as a small megatsunami. At the Osaki-bana point Futsu town, the waves locally grew to a height of 187 ft (57 m) due to the effect of sea bottom topography.