The Great Natchez Tornado was a tornado that hit Natchez, Mississippi on May 7, 1840. It is the second deadliest single tornado in United States history, killing 317 people (the only tornado to have killed more people was the Tri-State Tornado). It is also one of the only tornadoes in the United States to have killed more people than it injured: only 109 were injured.

The tornado formed southwest of Natchez and moved northeast along the Mississippi River. It then moved into the town of Natchez and destroyed many buildings. The final death toll was 48 on land and 269 on the river, mostly from the sinking of flatboats . The death toll is slightly disputed because of the land death toll of 48. It is believed that people died on plantations, and since this was pre-Civil War Mississippi, slave deaths weren't necessarily counted. The Fujita scale rating of this tornado is unknown since pre-1870 tornadoes were not given a Fujita scale rating.

It is also believed that if the tornado had hit Natchez at a different angle, it would have only been a footnote in weather history. There was nothing else of a similar magnitude until the Camanche, Iowa tornado of June 3, 1860.

See also: List of tornadoes and tornado outbreaks