Appointed governor of the new Indiana Territory in 1800, Harrison had the job of defending and extending white settlements, and he did so by going back into battle. In 1811, as the threat organized by the Shawnee Indian chieftain Tecumseh grew stronger, Harrison successfully led about a thousand men against a Shawnee uprising on the Tippecanoe River on Nov. 7. He earned the nickname "Old Tip," but more importantly the rank of brigadier general and was given command of U.S. forces in the Northwest.

In 1813, during the War of 1812, Harrison defeated a joint force of British and Indian fighters at the Battle of the Thames River, near Ontario, Canada. Tecumseh was killed, and the victory ended the Indian resistance in the Northwest for good. Harrison resigned from the Army in 1814 at the age of 41.