Harrison first joined the U.S. Army in 1791. He was an aide to General "Mad Anthony" Wayne in a battle against a coalition of native Americans, the Battle of Fallen Timbers. Harrison witnessed and signed the resulting treaty that forced the coalition to give up a large portion of territory for a meagre sum of money.

Harrison was appointed governor of Indian Territory in 1800. In 1804, a Sauk and Mesquakie delegation came to see him. They hoped to obtain the release of a warrior who'd been arrested for murder. Harrison wined and dined them until they were drunk. He then made them sign away 4.5 million hectares (10 million acres) of land. In 1809, Harrison also got the Delaware, Miami, Potawatomi, and Eel Nations to give up huge portions of their territories for relatively little in return.

In 1811, a Shawnee army attacked Harrison and his 800-man army at Tippecanoe Creek. Harrison fought them off but suffered heavy casualties. In 1813, at Moraviantown in Upper Canada, Harrison and his army defeated the British and their First Nations allies led by Tecumseh.

Harrison ran for the presidency of the United States in 1840. He won, but caught a cold at the beginning of his tenure. His cold worsened and turned into pneumonia. He died on March 4, 1841, 30 days after his inauguration.