Harrison's political career began in 1798, with an appointment as Secretary of the Northwest Territory; in 1799 he was elected as the territory's non-voting delegate in the United States House of Representatives. He became governor of the newly established Indiana Territory in 1801 and negotiated multiple treaties with American Indian tribes, with the nation acquiring millions of acres. After the War of 1812, he moved to Ohio where, in 1816, he was elected to represent the state's 1st district in the United States House of Representatives. In 1824, he was elected to the United States Senate, though his Senate term was cut short by his appointment as Minister Plenipotentiary to Gran Colombia in 1828.
Harrison returned to private life in North Bend, Ohio, until he was nominated as one of several Whig Party nominees for president in the 1836 presidential election; he was defeated by Democratic vice president Martin Van Buren. Four years later, the party nominated him again, with John Tyler as his running mate, under the campaign slogan "Tippecanoe and Tyler Too". 