The school's first president was Rueben Nelson, and in its first year, 138 students enrolled — 69 boys and 69 girls from Pennsylvania and New York.

[4] At the time, Kingston was a rural village, and the school raised livestock, grew its own produce, and built a smokehouse to preserve meat for the winter.

While the school remains affiliated with the United Methodist Church, it welcomes students from all religious backgrounds.

Much of Wyoming Seminary's rise from a rural academy to a prominent college preparatory school took place during the tenure of Levi Sprague.

By the early 1950s, Sem expanded to include what is today considered the "lower school", composed of nursery through eighth-grade students.

Sem also bought a former bank adjacent to its Upper School campus to become the Great Hall, used today by the wrestling team as its practice facility.

At the Lower School, similar changes were made, including constructing a new wing for fourth and fifth-grade students and a new glass foyer.

The Pettebone-Dickson Student Center, located on N. Maple Avenue, includes sports and administrative facilities.

The Great Hall is located on Wyoming Avenue and separate from campus, mainly used for sports and wrestling facilities.

The Lower School is mainly in one building, aside from back campus fields and a toddler learning center.

[8] Since 2006, portions of the Upper School campus have undergone a large-scale renovation, with the housing facilities of Swetland, Darte, and Fleck Halls renovated on the outside, the Kirby Library (on the second floor of the Stettler Center) renovated, a brand new third floor introduced in Sprague Hall, the construction of Klassner Field for field hockey and lacrosse games,[9] the construction of the O. Charles Lull Tennis Center and a brand new first floor of the Lower School.

The Kirby Center for Creative Arts, supporting the school's music, theater, and dance programs, was completed in the fall of 2014.