In 1885, the All Saints Hospital was opened at 10th and Campbell Streets with a training school for nurses being established in 1887. Saint Luke's Hospital was declared the legal successor of All Saints Hospital in 1903, and that same year the School of Nursing was established with three students under the direction of Miss Eleanor Keely. Miss Virginia Pate was the first graduate of the diploma program in 1906.
The 1920's brought many changes to the School of Nursing including relocation to a new hospital and a nurses' residence at the site, which was then Mill Creek and 44th Street. A four-story building was erected in 1946 to accommodate classrooms, laboratories, library, offices, and residence space for approximately 200 students. The library was moved to the Helen F. Spencer Center for Education in 1972, and the student residence was relocated to 4545 Washington Street in 1987.
The development of Saint Luke's College began during the 1985-86 academic year when the faculty of Saint Luke's Hospital School of Nursing made an in-depth study of the issues and challenges facing nursing education in the twenty-first century. Students’ and graduates’ reactions regarding the nationwide movement of nursing toward baccalaureate education, and the support of the Alumni Association were instrumental in establishing a plan for a program granting a Bachelor of Science in Nursing degree. The first class of students was admitted in the fall of 1991 for baccalaureate nursing education at Saint Luke's College. In 1992, the final class graduated from the diploma program culminating in 3,047 students having received their nursing diploma from Saint Luke's Hospital School of Nursing. As of 2010, 18 classes have completed coursework resulting in 867 graduates from the BSN degree program.
On August 29, 2010, the college was renamed Saint Luke’s College of Health Sciences in conjunction with a change to a private, not-for-profit, corporation status.