The history of Seattle University College of Nursing is linked to the early history of Providence Hospital in Seattle. In 1877, the Sisters of Providence responded to a request to care for those in the Seattle area who were sick and poor. The "Poor House" at 5th and Spring streets was eventually moved to 17th and Jefferson and became Providence Hospital. By 1907, seventeen Sisters of Charity of Providence were registered as nurses in the state of Washington. Needs for nursing care increased, and the Providence Hospital School of Nursing was opened July 16, 1907, with four lay students enrolled. The first class of the Providence Hospital School of Nursing graduated in 1910.

Today the College of Nursing resides in the completely renovated historic Garrand Building at the center of campus. This building, the oldest on campus, was the original site of Seattle College. It is located between the Administration and Casey buildings with entrances on the south and east sides. The building houses the Dean's office, faculty offices, and several conference rooms. A rededication of the building was held on December 8, 1994, with Archbishop Thomas Murphy officiating at a morning mass. In Fall 2003, the School of Nursing officially changed it's name to the College of Nursing reflecting the growth and complexity of its programs of study. Through the years, students and faculty have been important contributing members of this community.

On July 16, 2005 the community got its first look at the $65 million dollar renovation of the former Providence Hospital, which houses the Seattle University College of Nursing’s Clinical Performance Lab. The newly renovated and retrofitted building, a project of the Sabey Corporation, reopened as the James Tower Life Sciences Building. Within the new building, 19,000 square feet of space was set aside for the College of Nursing’s Clinical Performance Lab. The state-of-the-art facility houses research labs, classrooms, faculty offices and an exam clinic. The lab is made possible by the Jim and Janet Sinegal Initiative for Nursing Education, which gave the Seattle University College of Nursing $5 million to improve access to quality health care. The new lab seeks to replicate hospital and clinical settings, complete with patient simulators, giving students experience in a setting as close to the real thing as possible.