It serves the towns of Mendon and Upton through a cooperative arrangement established in 1961.

The school was named after the Nipmuc indigenous people of the area.

Nipmuc Regional High School sports include mixed cheer leading, cross country, football, Golf (men), soccer, field hockey, baseball, volleyball, lacrosse, track (indoor/outdoor), hockey, basketball, wrestling and swimming.

[10] The boys' soccer team won the Division 3 State Championship in 2017.

The student to teacher ratio in the school is 13:1[11] The participation rate for Nipmuc is 63%