The University of Iowa first lists "The Training School for Nurses" as a two year course in the 1896-1897 university catalog. Jennie S. Cottle was named the first superintendent of the hospital and principal of the Training School, with one student admitted in the fall of 1897. Five additional students were admitted with the opening of the new university hospital in 1898 and in 1900 the training program was extended to three years.

In 1906 the nursing students were moved from their hospital residence to a rented dwelling. In 1915 the nursing students occupied the Eastlawn residence until their move to the Westlawn nurses' residence five years later. Undergraduate nursing students resided there until 1964, when the building was remodeled into classroom and office spaces.

The School of Nursing was listed on the Iowa State Board of Health list of approved schools in 1908 and in 1919 the nursing program was established as a five year program that integrated liberal arts and nursing. Lois B. Corder and Lola I. Lindsey assumed administrative and educational direction of the School of Nursing in 1927. The Board of Regents appointed the first nursing faculty, Amy Frances Brown, as assistant professor in 1948 and within a year the Board moved to establish a collegiate program in nursing. Myrtle E. Kitchell was appointed director of the school in August 1949 and on December 3, 1949 she was installed as the first dean of nursing. The College of Nursing was thus formally inaugurated as the tenth autonomous college of the University of Iowa. In September of the same year the first class of students was admitted to the baccalaureate program in nursing.

In 1951, the general nursing program leading to a bachelor of science in nursing was established and a grant from the W.K. Kellogg Foundation made possible the first graduate program in nursing; the three year program leading to a certificate of graduate nursing was discontinued by 1955. Thirty-two students graduated as the first class to receive their bachelor of science in nursing degrees from the College of Nursing in 1953. By 1960 the graduating class swelled to one hundred and six students, and a four-year curriculum was approved by the Board of Regents. The general nursing program leading to a master of arts degree was approved by the Graduate College in 1958 and further revisions of the graduate program in 1961 resulted in three clinical nursing majors: medical-surgical, pediatric, and psychiatric nursing.

A three-year federal training grant in 1976 enabled the college to offer the medical-surgical major as an outreach graduate program and two years later another three-year federal training grant was used to revise and evaluate the graduate program and its curriculum, and to develop and implement an outreach model of graduate level courses. During the same year the revised graduate program that led to the MA degree was implemented. The master of arts degree was changed to a master of science in Nursing (MSN) in 1995.

Graduate work at the doctoral level was explored in a feasibility study in 1985 and the doctoral program was established that same year. As a result of its growth, the College of Nursing submitted two letters of intent to apply for a construction grant and a "General Statement of Building Needs" prior to its formal application for a construction grant in 1966. The grant was approved by the University administration the next year and the state provided matching funds. The building construction took two years with a ground breaking ceremony in October 1969 and the final dedication and occupation of the new College of Nursing building in December 1971.