Harrison was lured to the western frontier by the stories of the Indian wars that were happening. He was commissioned by President Washington as an ensign in the infantry. In 1791, he arrived at Fort Washington (Cincinnati) and soon became an aide to General Anthony Wayne. He fought in the Battle of Fallen Timbers with Wayne and was present when the Treaty of Greenville was negotiated.

New responsibilities soon followed. In 1799, he became a delegate to Congress and supported the sale of lands on the Ohio frontier. He was appointed governor of the Territory of Indiana and moved with his wife, Anne Symmes Harrison, to Vincennes. In his role as governor, Harrison proved his ability to skillfully negotiate with the Indians, concluding 15 treaties and over 60 million acres of land for settlement.

However, when a treaty could not be negotiated with the Indians, he fought once again. The Battle of Tippecanoe, in November 1811, was a notable victory for Harrison and his military reputation was further enhanced. He continued fighting for America against the British in the War of 1812 and his reputation continued to grow.

In 1814, there was no further threat from the British or the Indians. Harrison resigned his commission and returned to Ohio. His house was a regular stop for dignitaries visiting Ohio. He began his political career also when he was elected to the Ohio legislature.

In 1840, he was candidate for president and ran with the campaign slogan "Tippecanoe and Tyler too!" The 67 year old Harrison was elected president. After only a month in office, Harrison died of pneumonia.