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The origins of the OHSU School of Nursing can be traced to the summer of 1919 when the University of Oregon introduced the state's first professional courses in nursing. The courses were offered in Portland in cooperation with the Northwest Division of the American Red Cross Home Service Department, the Portland Visiting Nurse Association, the Welfare Bureau, and the Oregon Tuberculosis Association. During this time, the Portland School of Social Work offered a standard course of study in public health nursing.

In 1926, the University of Oregon, recognizing the need for baccalaureate prepared nurses, introduced a five-year curriculum culminating in the Bachelor of Science degree with a major in Nursing. Additionally, between 1928 and 1939, a certificate program was offered for qualified students in accredited hospital schools permitting them to receive university offerings facilitating their career mobility.

As a part of the 1932 reorganization of the Oregon State System of Higher Education, the Portland School of Social Work was integrated into the University of Oregon Medical School in Portland and a Department of Nursing Education was established. The University of Oregon Medical School, Department of Nursing Education offered courses using its own facilities and clinical resources at accredited community hospitals and agencies. Additionally, a 2-year pre-nursing curriculum was established at University of Oregon and Oregon State University. During World War II, the baccalaureate degree program was accelerated into a 4-year program, and public health nursing was incorporated into the program in 1956 under the guidance of Elnora Thomson, a leader in the field.

In 1947, a $60,000 grant from the W.K. Kellogg Foundation made possible a teaching and supervision program for baccalaureate prepared registered nurses which in 1955 became the Master of Science degree in nursing education.

The Oregon State Board of Higher Education, in 1960, recognized the changing nature of nursing and expanded the Department of Nursing Education to its current status as the School of Nursing. During the 1960s the school further developed its undergraduate and graduate program offerings. In 1961, funds from the U.S. Public Health Service supported a comprehensive study of mental health concepts in the baccalaureate program. The Nurse Training Act made possible additional areas of graduate study and increased undergraduate enrollment of registered nurses. The baccalaureate degree was further strengthened in 1972 by funding that developed a learning resources center. Other study and development grants assisted growth in various school programs, especially continuing education. The school began offering a Master of Nursing degree in 1971.