With the outbreak of war with England in 1776, Wayne was commissioned a colonel and assisted General Benedict Arnold in his retreat from Quebec. He held various positions with the Continental Army and shared with General George Washington the long winter of 1777-78 at Valley Forge. In 1779, Wayne and his troops captured the English garrison at Stony Point, N.Y.  Sent south in 1781, Wayne and his command were hemmed in by British General Charles Cornwallis' superior forces at Green Springs, Va., but managed to escape with his men. He then served under General Nathaniel Greene, helping to force the British out of Georgia and South Carolina in 1782.  

Wayne was recalled as a major general by Washington in 1792 and sent to take command in Ohio. Americans knew him as "Mad Anthony," but the Indians would call him "Blacksnake," because, like the blacksnake, Wayne sat quietly, patiently waiting for the right moment to strike. Wayne trained an army of regulars while building a line of forts aimed straight into the heartland of the alliance in northwest Ohio. As the alliance chiefs nervously watched Wayne's slow, methodical approach, American commissioners made overtures of peace. The British again urged resistance, and the Shawnee killed two American representatives enroute to a conference with the alliance. The alliance, however, was beginning to unravel. It could field 2,000 warriors but had trouble feeding them over an extended period, and Wayne was definitely extending the conflict. In 1792 the Wabash tribes (Peoria, Piankashaw, Kickapoo, and Wea) signed a treaty with the Americans which caused them to leave the alliance and remain neutral. The Fox and Sauk also withdrew at the same time.  

In July, 1793 American commissioners met for the last time with the alliance. At first, only the Wyandot, Shawnee, and Miami favored continuing the war, while the others were undecided. Finally, the majority decided to fight, and the meeting ended. In October Wayne received orders to begin an advance north from Fort Washington (Cincinnati). One of Wayne's supply trains was destroyed at Ludlow Spring, but he established himself at Fort Greenville (80 miles north of Cincinnati). As the  time of confrontation approached, doubts emerged within the alliance, and the Shawnee chief, Blue Jacket opened separate negotiations. The start of Wayne's advance may also have played a part in the British decision to finally close its forts on American territory and reach an accommodation with the United States. After a desperate attack on the Americans at Fort Recovery failed, the alliance had only 700 warriors in August, 1794 to face Wayne's Legion at Fallen Timbers. After the battle, the retreating warriors sought refuge with the British at Fort Miami, only to have them close the gates on their former allies.  

Wayne's army marched right up to the British fort but did not attack. Afterwards, the Americans burned several nearby Indian villages and destroyed their food supplies. Then Wayne returned to Fort Greenville and waited. After a hungry winter, the alliance made peace. No longer able to rely on British help against the Americans, the Wyandot and other tribes signed the Treaty of Fort Greenville in 1795 ceding all of Ohio except the northwest.  

After accepting the surrender of Detroit in 1796, General Anthony Wayne was seized with a severe attack of gout and died at Fort Presque Isle, Penn., Dec. 15, 1796.