Fort Wayne is located in the city of Detroit, Michigan, at the foot of Livernois Avenue in the Delray neighborhood. The fort is situated on the Detroit River at a point where it is about a mile to the Canadian shore. The original 1848 limestone barracks (with later brick additions) still stands, as does the 1845 star fortification (renovated in 1863 with brick exterior facing). On the fort grounds but exterior to the original star fort are additional barracks, officers quarters, hospital, shops, recreation building, commissary, guard house, garage, and stables. Building continued on the site until 1931.

The fort sits on 96 acres. Since the 1970s, 83 acres, including the original star fort and a number of buildings, has been operated by the city of Detroit. The remaining area is operated by the Army Corps of Engineers as a boatyard.

Fort Wayne is Detroit's third fort. The first, Fort Detroit, was built by the French in 1701. This fort, constructed shortly after Cadillac landed, was manned by the French until it was surrendered to the British in 1760 during the French and Indian War. The second fort, Fort Lernoult, was built by the British a few years later, and was manned by the British until 1796. When the United States took over Detroit, Fort Lernoult was renamed Fort Shelby.

During the War of 1812, General William Hull surrendered Fort Shelby to the British during the Siege of Detroit without offering any resistance. The British later abandoned the fort and American troops reoccupied it. However, following the end of the war, Fort Shelby fell into disrepair. In 1826, it was sold to the City of Detroit and demolished.

In the late 1830s, Canadian and American rebels organized to free Canada from the British, leading to a series of battles known as the Patriot War. American troops were mustered to suppress the American volunteers and maintain America's official neutrality in the conflict. However, at the same time, the United States government realized there were a lack of fortifications along the northern border to repel a potential British attack, and in particular, no counterpart to the British Fort Malden located in Amherstburg. In 1841, Congress appropriated funds to build a chain of forts stretching from the east coast to the Minnesota Territory, including one at Detroit.

Soon afterward, the Army sent Lieutenant Montgomery C. Meigs to Detroit. Meigs bought up riverfront farm property three miles below Detroit, at the point on the Detroit River closest to Canada. Construction on the fort began in 1843, with Meigs superintending. The original fortifications were cedar-faced earthen walls. The fort was completed in 1851, costing $150,000. The Army named the new fort for Revolutionary War hero General "Mad" Anthony Wayne, who had taken possession of Detroit from the British in 1796.