The Nipher Middle School building was built in 1921 and officially opened in September 1922 as the community's new high school. Before its construction, secondary students had attended school with elementary-age children in one of the district's first buildings, a four-room brick school built in 1869 at Adams and Jefferson. A few years after the high school opened on Kirkwood Road, a separate south building was built in 1929 to house seventh and eighth grade students in a junior high school.
Following the tradition of naming public schools for outstanding community citizens, the Board of Education chose to name the junior high school in honor of Dr. Francis E. Nipher, who had been a distinguished educator and professor at Washington University in St. Louis. The north building housed Kirkwood High School until its move in 1954 to its present location on Essex.
During reorganization in 1976, Nipher Junior High School became Nipher Middle School to house Grades 6 through 8 with Grade 9 moving to Kirkwood High School.
Renovations resulting from a 1993 bond issue included construction of a two-story addition to house a new library/media center, three computer classrooms, three regular classrooms, the main school and counselors' offices as well as technology infrastructure, air conditioning, ventilation system improvements, stage renovation and interior upgrades.
In 2005, the community approved Proposition I, a two-part bond initiative that provided funds for improvements and infrastructure repairs throughout the district as well as funds to complete the district’s master facilities plan. Prop I improvements at Nipher include new water/fire main, new fire alarm, exterior door replacements, exterior painting, slate roof repairs, and gym floor restoration.
The Nipher building is a historical landmark and recent additions and improvements continue to reflect the original design of William B. Ittner, renowned school architect.