Located in the heart of the largest Concord grape-growing region in the world on the shores of Lake Erie, Mercyhurst University's North East Campus was founded in 1991 on an 84-acre site that was once home to the St. Mary’s Seminary. For more than 25 years, students chose Mercyhurst North East as a place to gain an education as either the start of a bachelor's degree or to find immediate employment. MNE offered 24 academic programs, including 17 associate degrees, six certificates and one allied health bachelor's degree.

The founding of MNE was inspired by the mission of the Sisters of Mercy, who believe that education should be available to all students. All associate degree students may apply to continue their studies at Mercyhurst's Main Campus in Erie, which offers more than 60 bachelor's degree programs, as well as more than 25 graduate programs.

The Mercyhurst North East campus was home to the College of Our Lady of Perpetual Help, also known as St. Mary's Seminary, for 110 years before the seminary closed its doors in the mid-1980’s. For five years, the 84-acre complex sat empty while prospective buyers considered it for a senior citizen complex, a correctional facility ,and the production site for horror films. But the Fathers wanted to ensure that the rich educational history of the site would be carried into the future, so they approached Mercyhurst about purchasing the property.

Until college trustees voted on the matter, North East businessman Robert Miller put a $50,000 deposit down to hold the facility, and the North East community raised $500,000 toward its renovation. Mercyhurst North East opened its doors in 1991 as an "opportunity and career college" dedicated to providing post-secondary education for capable learners who seek to learn job-entry skills. In essence, the goal was to fulfill a community college role in the Mercyhurst tradition.

The original mission of Mother Catherine McAuley, founder of the Sisters of Mercy, was to assist those who were interested in improving their lives. Mercyhurst North East extended the Mercyhurst University motto of "Carpe Diem" ("Seize the Opportunity") by offering an accessible and affordable post-secondary education focused on associate degree and certificate education. Giving opportunity and support to those with a sincere desire to improve themselves exemplified the tradition of the Sisters of Mercy and encourages a greater spectrum of individuals to avail themselves of a post-secondary education in a private college environment.

In 2019, Mercyhurst University announced the "Mission Inspired. Future Ready." initiative, comprised of a multi-year plan to strengthen its two-year and four-year health care programs and consolidate all academic programming to the main campus in Erie, Pennsylvania, by June 2021. In the wake of the COVID-19 pandemic, this campus consolidation timeline was accelerated in May 2020 to relocate all programs — with the exception of the nursing, allied health, biology, and municipal police programs — to the main campus by Fall 2020 and transition Mercyhurst North East to serve as a North East instructional site.