The idea of opening a College of Nursing was conceptualized in 2002 during presidency of Fr. Jimmy Belita, CM. Dr. Rosario Alberto, then Vice President for Academic Affairs; Dr. Myrna Añes, former Dean of the College of Science and Bro. Henry Escurel, then University Registrar, led the initiative, paving the way for the college's curricular offerings and eventual establishment.

After initial approval in 2002, the College underwent evaluations from the Regional Quality Assurance Team under Dr. Añes' deanship. Initially a department under the College of Science, the College of Nursing was granted a one-year operation permit in February 2003. However, the newly minted College of Nursing was asked to have a dean who has a bachelor's degree in Nursing for it to be allowed to function independently. Hence, Fr. Dionisio Abuel, CM, a Vincentian priest and Registered Nurse, became the first dean of the College, although his tenure was short-lived. This led the College to find a successor who has a bachelor's and master's degree in Nursing, as well as experience in both clinical practice and academia.

Dr. Leah Primitiva Samaco-Pacquiz was the dean when the Adamson University College of Nursing officially opened in 2003 with 606 students and four (4) faculty members. Almost a year after the term of Dr. Pacquiz, Mrs. Flora May B. Famadico assumed the position in the first semester of 2005. It was under her administration that the first Nursing Aptitude Test (NAT) was held to maintain the high standards of the college.

This commitment to academic excellence and quality education was further enhanced by Dean Naressia Seludo-Ballena in 2005 through strict implementation of the 2005 nursing curriculum and hiring of competent and dedicated faculty members to ensure the delivery of excellent nursing education.

Affiliating institutions also grew in number with the inclusion of hospitals such as St. Victoria Hospital, Antipolo City Medical Center, Gat Andres Medical Center, Dasmariñas Lying-in Clinic, and specialized institutions like Philippine Orthopedic Center, National Center for Mental Health and San Lazaro Hospital to assist the students in acquiring the essential nursing skills and workplace attitude through their exposure to related learning experience in nurse-patient care.

The college made a mark in the history of Adamson University when the first batch of Vincentian nurses attained a 90.82% passing rate in the Nurse Licensure Examination (NLE) in 2007.

Dr. Almira Tenorio was appointed Officer-in-Charge to oversee the acceptance of transferees and shifters to the College during the transitional period caused by a shift in the educational system. Dr. Tenorio was eventually seated as dean wherein she spearheaded the application of the Outcome-Based Education (OBE) curriculum to the College of Nursing in 2018.

Today, the Adamson University-College of Nursing, remains dedicated to providing quality education and shaping world-class and socially responsible healthcare providers inspired by the teachings of Saint Vincent de Paul.