Unlike many American commanders during the War of Independence, Wayne had no military experience before the fighting began. He had been active in local politics in Pennsylvania before 1775, which gained him an appointment as colonel of a regiment of Pennsylvanian line infantry in the Continental army in January 1776. He was soon sent with his regiment to reinforce the invasion of Canada, but that expedition had already failed when they arrived, just in time to play a prominent part in the American defeat at Three Rivers (8 June). They then covered the retreat to Ticonderoga, where Wayne spend several months commanding the garrison in a period when the British were expected to attack it, but in the end decided not to do so.
Wayne was promoted to brigadier-general in February 1777, and the next month joined Washington's army at Morristown as commander of the Pennsylvania Line infantry. Once again he arrived in time to see combat, this time the unsuccessful American defence of Philadelphia. At Brandywine (11 September 1777) his infantry held well until the British flanking attack forced an American retreat. Left to harass the British advance while Washington regrouped the main army, Wayne was guilty of failing to set adequate sentries on his camp at Paoli, and the British were able to take advantage (Paoli Massacre, 20-21 September 1777). He returned to the main army, which continued to take harass the British even after the fall of Philadelphia. He was again prominent in attack at the battle of Germanstown (4 October 1777), demonstrating his aggressive attitude to the war. Following Germanstown, Wayne followed Washington went into winter quarters at Valley Forge, where despite the atrocious conditions the Continental Army began to train properly. From Valley Forge he led foraging expeditions into New Jersey where he was increasingly successful in his efforts.
1778 saw the Continental Army remain inactive until the early summer, when the British decided to withdraw from Philadelphia. Wayne was one of the few officers to advocate an attack on the British before they could begin their march, but it was only after Clinton had begun his move that Washington decided to follow. Wayne's infantry played a creditable part in the otherwise inconclusive battle of Monmouth, where he helped Washington restore order after early disasters (28 June 1778) and once again advocated an aggressive pursuit after the battle, again overruled by Washington.
Towards the end of 1778 Wayne was rewarded for his service with his own command, of a brigade of light infantry 2000 strong from the Continental Army. The following year this unit played an important part in defeating a British attempt to capture the New York Highlands, capturing the very strong British position at Stony Point after his brigade managed to very nearly surprise the defenders, but were still able to overwhelm the British defenders in twenty minutes of hand to hand fighting (15 July 1779). However, the position was soon abandoned after the defences were destroyed.
1780 saw little action around New York. Wayne's command was eventually disbanded, but not before Wayne was able to foil Benedict Arnold's attempt to betray West Point to the British by moving his command into the fort (25 September 1780). The end of 1780 and the early part of 1781 saw several mutinies amongst American units, including the Pennsylvania Line, which mutinied in December 1780. It was Wayne who took their complains to Congress where he successfully made their case.
Arnold was now sent to the Chesapeake, where in January 1781 he successfully captured and destroyed Richmond (Virginia). Washington's response was to send 1,200 men under Lafayette to cooperate with the local militia and French forces. Wayne was part of that force, which later in the year was to take part in the Yorktown campaign. Cornwallis had spent the spring of 1781 attempting to pacify South Carolina, but by the end of May he had returned to Virginia with one of his aims an attack on Lafayette. Cornwallis managed to ambush the van of Lafayette's army at Greenspring (6 July 1781), commanded by Wayne, and routed it. Despite this, Lafayette was able to keep Cornwallis off balance and prevent any further American defeats. Lafayette's army was soon joined by Washington and Rochambeau in the campaign that led to the surrender at Yorktown.
Although the Yorktown surrender effectively ended the war, the fighting did not immediately stop. In January 1782 Wayne, along with Nathaniel Greene, was sent into Georgia, where the British were still relatively strong, with orders to force the British back into Savannah. His campaign was disrupted by expiring enlistments, as well as strong Loyalist and Indian forces opposing him, but he was able to establish a base at Ebenezer, only 25 miles from Savannah, in February. However, the campaign bogged down - Wayne never became strong enough to tackle the British position at Savannah, while the British themselves expected to be withdrawn and so were themselves largely inactive. The order to leave Savannah arrived on 14 June 1782, and on 11 July the British left and Wayne marched in.
After the war, Wayne returned to private life for a decade. Congress was opposed to the idea of a national standing army, hoping to rely on local militias. After a brief period where the army was cut down to under one hundred men, a single regiment was raised. In 1790 and 1791 this regiment suffered two crushing defeats at the hands of the Miami Indians in the Ohio Valley. Congress now decided to raise a new permanent force, and President Washington called on his old subordinate Wayne to command it.
The new American Legion mustered near Pittsburgh, where Wayne spent some time turning the 3,600 men of the new force into a well training, if small, army. Finally, in 1794 the Legion was ready, and Wayne marched them into the Ohio wilderness. This time the march was a well organised affair, unlike the previous two. Wayne protected his line of march with a series of forts, one of which, Fort Recovery, was attacked on 29 June and successfully defended. Finally, Wayne caught up with the main Indian force at Fallen Timbers. He then waited three days, during which time the Indian force began to shrink, before launching his attack on 20 August 1794. The Legion performed well in the battle, routing the Indian force for very little lose, before going on to destroy several local Indian villages. The next year saw Wayne involved in the peace negotiations that resulted in the Miami submission in August 1795.
Wayne remained on active duty, dying on 15 December 1796 while returning from a new outpost that had been established at Detroit. From a soldier whose main attribute had been his courage under fire, Wayne had matured into a careful leader whose final campaign was a model operation.