Professor Joseph McMurran was appointed the first principal of the institution, which opened with 42 students in September 1871, under the authority of the board of trustees.

On February 27, 1872, the Legislature of West Virginia passed the following act: “That a branch of the State Normal School be and it is hereby established at the building known as Shepherd College, in Shepherdstown, in Jefferson County.” Shepherd became a four-year college for the training of teachers on July 1, 1930, at which time the institution began granting the bachelor of arts degree.

The $21.6 million Wellness Center opened on June 11, 2009, and includes a 25-yard, eight-lane pool; two basketball courts, and six basketball hoops; two racquetball courts; an indoor elevated 1/10-mile jogging track; two multi-purpose rooms with mirrored walls for group exercise classes; a 7,500+ square foot weight and fitness area; and a dining venue operated by Shepherd's Dining Services.

The 46,000-square-foot (4,300 m2) expansion, dedicated in 2002, includes multimedia classrooms, additional reading areas and seating, and the Robert C. Byrd Center for Congressional History and Education whose purpose is to promote an understanding of the United States Congress and the Constitution through public programing, teacher training.

The plays are professionally produced using Actors' Equity Association's LORT D contract; CATF operates under agreements from AEA, United Scenic Artists, and the Society of Stage Directors and Choreographers.

Once completed, a simple query will be able to provide a very accurate total for both sides including data heretofore unavailable to historians.

Additionally, the Stubblefield Institute hosts Community Engage Conversations, public forums focusing on local and West Virginia issues.

Shepherd fields 15 intercollegiate teams: Men's sports include baseball, basketball, cross country, football, golf, soccer and tennis; while women's sports include basketball, cross country, golf, lacrosse, soccer, softball, tennis and volleyball.

The Ram marching band, cheerleading squad, and dance team promote spirit at university home games.

In 2015, Shepherd advanced to the NCAA Division II football national championship game, losing to Northwest Missouri State University 34–7.

In 2019, the Rams reached the NCAA Division II playoffs and lost in the second round to Slippery Rock University of Pennsylvania 50–31.

[13] On December 17, 2021, Junior QB Tyson Bagent won the Harlon Hill Trophy, awarded to the player of the year in Division II.

On October 22, 2023, Tyson Bagent became the first Division II undrafted rookie since 1950 to start an NFL game (with the Chicago Bears).