[4] Melvindale began as the unincorporated settlement of Oakwood Heights in the northwestern part of Ecorse Township in the early 1920s.

[5] The subdivision was designed to house workers from the nearby Ford River Rouge Plant in the city of Dearborn.

The city was named after one of the original developers of the settlement, Melvin Wilkinson.

[5] The eastern part of Oakwood Heights was annexed by the city of Detroit in 1922, and the remainder was incorporated as the village of Melvindale the same year.

[6] Melvindale serves an important role for railroad traffic in Metro Detroit.

The Norfolk Southern Railway Oakwood Yard, located along its Detroit District, divides the city into northwest and southeast sides.

The Canadian National Railway Dearborn Subdivision serves as the city's western boundary, and the Conrail Shared Assets Lincoln Secondary, serving as a direct route between Detroit and Toledo, Ohio for CSX Transportation trains, passes through industrial areas in the far southeast corner of the city, which is also the location of the remnants of the Conrail Lincoln Yard.

In 2005 the Roman Catholic Archdiocese of Detroit announced that St. Mary Magdalen Elementary School in Melvindale would close.