The Ruthruff School began as a one-story wooden one-room schoolhouse built in 1858 in then-rural Greenfield Township. Its site had 123 feet of frontage on what is now West Chicago Boulevard and 251 feet on the west side of what is now Livernois Avenue, and cost $1,300. A one-story, brick, one-room schoolhouse replaced it in 1885. It was the only permanent school building in District No. 10 of Greenfield Township before its annexation to the City of Detroit in 1916.

Its name dates back to the farmstead across the street belonging to William Ruthruff, whose farmhouse was located on the corner of Stoepel Avenue and West Chicago Boulevard. Ruthruff was a member of the Greenfield School Board until it came under the control of the City of Detroit. He died in 1921.

By 1916, the area around Ruthruff School was growing steadily. The district was changed from a primary school district to a graded school district, in the area referred to as the "Howlett" community. Two rooms were added, as well as some temporary rooms, before it was torn down in June 1923 after the Northwest Improvement Association requested more adequate facilities.

On Jan. 27, 1925, plans were presented to the Board of Education for the erection of a two section, two-story brick building. The building was designed in the Tudor Revival style by the firm McGrath, Dohmen & Page. The first section was completed in September 1925 and the second added at a later date. The Board of Education voted to retain the Ruthruff name.

Ruthruff School is a small building designed for a site that could not accommodate many extensions. It was designed for two sections, the first of which was completed in 1925. Its first and second story floor plans were published in the school board's Annual Report for that year. It was planned to house a complete twelve section platoon school. The layout of this first section is basically a lateral corridor with rooms opening off of it. This included a two-story tall gymnasium and a kindergarten on the first floor, an addition to the Science room, Literature room, Music and art room, one home room and a Conservatory.

Five additional home rooms, auxiliary rooms to the gymnasium such as showers, and an auditorium occupy the second story. The auditorium was situated directly above the large kindergarten room in the back corner of the building. The new building cost $177,263 and had a capacity of 620 pupils when it opened.

In 1927, two stores were leased for additional space adjacent to the school building because of increased enrollment. Its playground size was enlarged when lots on Livernois were purchased and houses were torn down.

Its second section containing six rooms was added in 1930. It was a six-room addition built at a cost of $63,048 to accommodate 160 more students. This addition brought the peak enrollment of the school to 825. Ruthruff School then had the distinction of having the largest Parent Teacher Association in the system, it having been organized in 1922.

In the 1980s and '90s the school was home to the Ruthruff Adult Education program. Starting around 2000, it housed the African-centric Malcolm X Academy. The school was closed in 2006, and leased a year later to the Last Chance Academy. The academy moved out in 2010, and the building was abandoned and left to the scrapper and elements to rip apart. It remained owned by the Detroit Public Schools district until 2014, when DPS transferred ownership of the property to the City of Detroit, one of 57 vacant DPS properties given to the City in exchange for wiping millions of dollars in DPS debt from unpaid electrical bills. The 32,000-square-foot school sits on 2.14 acres of land and is located in the Midwest neighborhood in Council District 6.

In 2021, the City released a report that offered potential developers insight into the structural integrity and floor plans of more than 60 vacant schools - 39 owned by the City and two dozen still owned by the school district. The effort was not only to take inventory of the dozens of vacant schools littering the city, but also to incentivize redevelopment of the structures by reducing the upfront costs through the assessments provided. Out of those schools studied for the redevelopment effort, Ruthruff was ranked 24th in terms of building condition. Redevelopment was estimated to cost about $8.7 million.

Finding no takers, the school was added to the City of Detroit's demolition list in August 2023 as part of the City’s "blight to beauty initiative." In late February 2024, a demolition fence was erected bearing signage for Homrich Demolition and stating that the building was undergoing demolition. As of Feb. 22, remediation appeared to have begun. By April 12, 204, half the school was rubble, with the last of it coming down April 17.