The Great Hurricane of 1780, also known as Huracán San Calixto, the Great Hurricane of the Antilles, and the 1780 Disaster is probably the deadliest Atlantic hurricane on record. Between 20,000 and 22,000 people died when the storm passed through the Lesser Antilles in the Caribbean starting on 10 October and ending on 16 October. Specifics on the hurricane's track and strength are unknown since the official Atlantic hurricane database only goes back to 1851.

The hurricane struck Barbados with winds possibly exceeding 320 km/h (200 mph), before moving past Martinique, Saint Lucia, and Sint Eustatius; thousands of deaths were reported on the islands. Coming in the midst of the American Revolution, the storm caused heavy losses to British and French fleets contesting for control of the area. The hurricane later passed near Puerto Rico and over the eastern portion of Hispaniola (then Santo Domingo, now the Dominican Republic). There, it caused heavy damage near the coastlines. It ultimately turned to the northeast before being last observed on October 20 southeast of Cape Race, Newfoundland.

The death toll from the Great Hurricane alone exceeds that of any other entire decade of Atlantic hurricanes, and is marginally higher than that of the second-deadliest Atlantic storm, Hurricane Mitch, although the figures for its death toll are estimates and Mitch numbers are probably much more accurate. The hurricane was part of the disastrous 1780 Atlantic hurricane season, with two other deadly storms occurring in the month of October.