In 1914, University of Minnesota president Dr. George E. Vincent approached Drs. William and Charles Mayo to form a partnership that would combine the educational offerings of the Mayo Clinic in Rochester with the Mayo Clinic School of Graduate Medical Education (MCSGME) at the University of Minnesota.

In 1915, the Mayo Foundation for Medical Education and Research was established and endowed with $1.5 million to support general medical and surgical education and research. The school offered more than 300 residences and fellowships in all medical and surgical specialties with 1,791 active trainees.