Harrison attended Hampden-Sydney College and studied medicine briefly under Benjamin Rush in Philadelphia before joining (1791) the army and taking part in campaigns against Native Americans in the Northwest Territory. In 1798 he resigned to become secretary of the territory, and the next year he became territorial delegate to Congress. He helped secure the division of the territory into Ohio and Indiana and served (1800–1812) as governor of Indiana Territory at Vincennes. He was perhaps more important than any other man in opening Ohio and Indiana to settlement, negotiating a number of treaties with various tribes, notably the Treaty of Fort Wayne (1809). Native American opposition to the white advance then concentrated in hostile demonstrations directed by Tecumseh. Harrison engaged the forces of Tecumseh at the famous battle of Tippecanoe.
In the War of 1812, after the failure of Gen. William Hull, Harrison was made commander in the Northwest. Taking Detroit (Sept. 29, 1813), he advanced to defeat Gen. Henry Procter and establish American hegemony in the West at the battle of the Thames River on Oct. 5, 1813 (see Thames, battle of the), in which Tecumseh was killed. Later Harrison concluded treaties with Native Americans—Greenville (1814) and Spring Wells (1815)—that ushered in an era of peace and white expansion in the Old Northwest. He served in the House of Representatives (1816–19) and the Senate (1825–28). He was appointed (1828) minister to Colombia but was recalled (1829) by Andrew Jackson. His political fortunes rose as he became regarded as a compromise Whig candidate between Henry Clay and Daniel Webster.