Col. William Wilkins was a veteran of the Civil War and member of the Detroit School Board. The first Wilkins School was built in 1873 on Porter street near downtown but was later torn down. As the population grew on the northeast side of the city, several portable classrooms were built in 1923. Construction on a permanent school building began in 1924, and the first unit of the new Wilkins School opened in February of 1925. A second unit was built in 1926, with total enrollment topping 1,230 students.
At some point the facade of Wilkins was extensively modernized, with much of the cornice removed and the windows completely replaced. The neighborhood around Wilkins steadily declined through the 1990's and 2000's. Crime in the neighborhood was an ongoing problem; in December of 2010, students walking to school found a body on fire on the side of Nashville Road.
Originally, Wilkins and nearby Flemming Schools were to be replaced with a new school to be built on the Osborn campus, but both stayed open. Fleming became an childhood education center, and Wilkins remained open until 2013 when it closed due to low enrollment and the poor condition of the facility.