The school was founded in 1885 by the Sisters of Charity. It is named for Elizabeth Ann Seton (1774–1821), who founded the Sisters of Charity and who, after her death, was canonized as the United States' first native-born saint. (Seton Hall University and Saint Elizabeth University in New Jersey are also named after Elizabeth Ann Seton.)
In 1914, Seton Hill Junior college was opened by the Sisters of Charity. With the approval of the Commonwealth of Pennsylvania, Seton Hill College was created four years later.
In 1946, 40 male World War II veterans were accepted as students at Seton Hill. During the 1980s, men were regularly admitted to many programs at Seton Hill College, including music and theater. In 2002, Seton Hill was officially granted university status by the Pennsylvania Department of Education.
Seton Hill University received widespread public attention after announcing a technology plan that includes providing an iPad to all full-time students, as well a 13" MacBook to all incoming freshmen. Upon graduation, students keep both devices. Beginning in the fall of 2013, new full-time students will receive an iPad Mini and new full-time freshmen will be provided with a MacBook Air. Seton Hill University is recognized as an Apple Distinguished School.