In March 1814, General Jackson's army left Fort Williams on the Coosa, cut a 52-mile trail through the forest in three days, and on the 26th made camp six miles north of Horseshoe Bend. The next morning, Jackson sent General John Coffee and 700 mounted infantry and 600 Cherokee and Lower Creek allies three miles down-stream to cross the Tallapoosa and surround the bend. He took the rest of the army - about 2000 men, consisting of East and West Tennessee militia and the Thirty-ninth U.S. Infantry - into the peninsula and at 10:30 a.m. began an ineffectual two-hour artillery bombardment of the Red Sticks' log barricade. At noon, some of Coffee's Cherokees crossed the river and assaulted the Red Sticks from the rear. Jackson quickly ordered a frontal bayonet charge, which poured over the barricade. Fighting ranged over the south end of the peninsula throughout the afternoon. By dark at least 800 of Chief Menawa's 1,000 Red Sticks were dead (557 slain on the field and 200-300 in the river). Menawa himself, although severely wounded, managed to escape. Jackson's losses in the battle were 49 killed and 154 wounded, many mortally.

Though the Red Sticks had been crushed at Tohopeka, the remnants of the hostile Creeks held out for several months. In August 1814, exhausted and starving, they surrendered to Jackson at Wetumpka, near the present city of Montgomery, Alabama. The Treaty of Fort Jackson ending the conflict required the Creeks to cede some 20 million acres of land - more than half of their ancestral territorial holdings - to the United States. The state of Alabama was carved out of this domain and admitted to the Union in 1819.

In 1829, partly as a result of his fame from the battles of Horseshoe Bend and New Orleans, Andrew Jackson was elected President of the United States; a year later he signed the Indian Removal Bill forcing all the tribes east of the Mississippi River to move to Oklahoma, a journey the Cherokees called the "Trail of Tears." The Southeast, cleared of most Indians and free from the threat of foreign intervention, thus became part of the United States and was opened for settlement.