Garfield High School opened its doors to students in September 1925. Located in unincorporated East Los Angeles, the campus was created to serve the new residential communities established in the early 1920s on formerly agricultural land east of the L.A. boundary. 

The campus is bordered by E. Sixth and Escuela Streets on the south and north, and by Woods and Fraser Avenues on the east and west.

Garfield High garnered national attention for the role it, along with four other Los Angeles high schools, played in the East L.A. Chicano Student Walkouts (Blowouts) of March 1968.

In 2018, the National Trust for Historic Preservation included the five Walkout schools, including Garfield High School, on America's 11 Most Endangered Historic Places list.