Mother M. Bernardina, founder of the Order of St. Francis in Syracuse, was a teacher in Utica and founded the hospital to care for its residents.

In December 2011, the Boards of Directors for Faxton St. Luke's Healthcare and St. Elizabeth Medical Center passed a resolution to begin discussions on the feasibility and benefits of merging or undertaking other transactions that would more closely link the two hospitals.

In December 2013, the Attorney General of New York announced a settlement addressing competitive concerns and allowing the affiliation to move forward.

[9] On March 6, 2014, Faxton St. Luke's Healthcare and St. Elizabeth Medical Center announced their affiliation under the Mohawk Valley Health System.

[14] As early as 2014, the same year MVHS was established, the organization began exploring the potential for a new hospital to replace the three existing campuses.

[21] An issue with an air handling unit on the second floor was discovered shortly before opening: MVHS and the New York State Department of Health determined that the move should continue as planned.

[30] Early in June 2024, physician assistants were temporarily barred from performing invasive procedures while MVHS confirmed their credentials.

[31] At the end of 2024, the former director of medical staff services filed suit against MVHS, claiming she was terminated and retaliated against for exposing lapses in credentialing.

[32] MVHS closed its Adult Day Health Care program on June 7, 2024, citing staffing challenges and declining patient demand.

The MVHS chief medical officer attributed the diversion to seasonal illness, winter accidents, and a large number of stroke patients.

A Utica city councillor pointed to inadequate staffing instead, common to other upstate hospitals, and put forward a resolution requesting assistance from the New York National Guard, as they had during the COVID-19 pandemic.