The site of Wayne was crossed by the Sauk Trail, and due to this, the area was visited by Potawatomi and French fur traders for years before permanent settlement.

The first settler was George M. Johnson, who built a small log cabin on 80 acres of land in 1824 (a state historical marker can now be found at the site).

[6] After a few years, the tavern was sold to Stephen G. Simmons, who continued to operate the business until he murdered his wife while in a drunken rage.

In 1832, Ezra Derby bought the tavern and land from the Simmons heirs and began establishing a settlement.

Derby built a sawmill, store, mill, blacksmith shop and the first frame dwelling for himself.

Soon a small hamlet began to develop, which was accelerated by the arrival of the Michigan Central Railroad in 1838.

The Gotfredson Truck was produced from 1924 to 1927, and The Graham-Paige car company made vehicles in Wayne from 1928 to 1936.

Stinson Aircraft was also located at the nearby Detroit Industrial Airport and produced small planes from 1926 to 1948.

The population and industrial production around Wayne significantly increased after World War II.

[8] The 1960s saw a period of urban renewal in downtown Wayne, as the city sought to compete with its neighbors.

As part of the redevelopment of the downtown area, Michigan Avenue received new eastbound lanes, routed one block south of Main Street along Norris Street, with the original undivided route retaining westbound traffic.

The redevelopment ultimately did not result in the kind of growth the city had hoped for, though; in particular, the undersized Town Square Plaza could not compete with the larger Westland Shopping Center a few miles north.

According to the United States Census Bureau, the city has a total area of 6.02 square miles (15.59 km2), all land.