William Henry Harrison was appointed governor of the newly formed Indiana Territory in 1800, and he sought to secure title to the area for settlement. The leader of the Shawnee, Tecumseh, opposed the 1809 Treaty of Fort Wayne. He believed that land was owned in common by all tribes; therefore specific parcels of lands could not be sold without full agreement from all the tribes. Though Tecumseh resisted the 1809 treaty, he was reluctant to confront the United States directly. He traveled through tribal lands, urging warriors to abandon their chiefs to join his effort, threatening to kill chiefs and warriors who adhered to the terms of the treaty, building a resistance at Prophetstown.

Tenskwatawa stayed with the Shawnee who were camped at the Tippecanoe in Prophetstown, a settlement that had grown to a few hundred structures and a sizable population. Harrison believed military force the only solution towards militant tribes. Harrison started raising troops. About 400 militia came from Indiana and 120 cavalry volunteers from Kentucky, led by Kentucky's U.S District Attorney Joseph Hamilton Daveiss. There were 300 Army regulars commanded by Col. John Parker Boyd, and additional native scouts. All told he had an about 1,000 troops.

Early the next morning warriors from Prophetstown attacked Harrison's army. They took the army by surprise, but Harrison and his men stood their ground for more than two hours. After the battle, Harrison's men burned Prophetstown to the ground, destroying the food supplies stored for the winter. The soldiers then returned to their homes.

Tecumseh continued to play a major role in military operations on the frontier. By the time that the U.S. declared war on Great Britain in the War of 1812, Tecumseh's confederacy was ready to launch its own war against the United States – this time with the British in open alliance.