On December 21, 1950, the voters of Auburn, California approved a bond for $215,000 for the construction of a new school. The passing of the bonds was largely due to the efforts of Auburn Union School District Superintendent Edgar Virgil Cain. The school was needed to overcome the overcrowded conditions in the school district. The district had more than 750 students at on school. In December of the next year, they approved an additional $41,000 for additional units for the school. (Auburn Sesquicentennial Research Committee, 1998) In 1952, the Palm Avenue School opened its doors. It was a fifth grade to eighth grade school with one fourth grade class added soon after its opening. Cain died in 1952, three years after the school was built and nine years after coming to Auburn. Palm Avenue School was renamed E.V. Cain Middle School after his death.
The school underwent building improvements, include a new gymnasium, in time for the start of the 2000 - 2001 school year. Shortly after the new school year began, former E.V. Cain Wildcat Stacy Dragila won the first ever gold medal for women's pole vault at the 2000 Olympic Summer Games in Sydney, Australia. In honor of her achievement, the new gymnasium was renamed the Dragila Gym.
While the school has always had 7th and 8th graders on its campus, the other grades moved around the district as new elementary schools were being added to the school district. The improvements on campus include the addition of a 6th grade area, known as the 6th grade village on campus, allowed the return of 6th graders from the district's elementary school to the E.V. Cain for the 2001 - 2002 school year. Enrollment blossomed from 644 to 1,031 students and has gradually settled to an average student population of about 750.
The school's current name, E.V. Cain STEM Charter Middle School, is the result of the the school's conversion to a Science-Technology-Engineering-Math charter school.