The College was established in principle at the inception of the University in 1970. Formerly known as the Faculty of Medicine and Pharmacy at a time when it constituted these two disciplines only, the College of Medical Sciences derived its name in 1975 from an amendment to the Edict establishing the University of Benin. The College is now composed of three Schools and one Institute. The Centre of Excellence in Reproductive Health Innovative (CERHI) is a recent addition; it is however, a World Bank Project awarded to the University of Benin.

The School of Medicine is the oldest of the Schools and has always been an integral part of the College since the foundation of the University and has the largest number of Departments. Currently, the School has seventeen (17) Departments namely: Anaesthesiology, Chemical Pathology, Child Health, Community Health, Haematology, Medical Microbiology, Medicine (Internal), Mental Health, Obtertrics and Gynaecology, Ophthalmology, Pathology (Morbid Anatomy), Radiology, Surgery,  Orthopaedics and Traumatology, Clinical Pharmacology and Therapeutics, Ear, Nose &Throat and Family Medicine.

Although the College was created in 1975, the School of Dentistry admitted its first set of Students and took off in 1977. Currently, the School has six (6) Departments namely: Preventive Dentistry, Restorative Dentistry, Periodontics Dentistry, Oral Diagnosis and Radiology, Oral and Maxillofacial Surgery and Oral and Maxillofacial Pathology and Medicine.

The School of Basic Medical Sciences (SBMS) was created in 2004 and admitted its first batch of Students into the basic medical sciences program in 2005. This school has grown rapidly and runs degree and Post-Graduate Programmes in Anatomy, Medical Biochemistry, Medical Laboratory Science, Nursing Science and Physiology. Recently, first degree Programmes were started in Physiotherapy and Radiography.

The Institute of Child Health is almost as old as the School of Medicine, having been established in 1972. It is a Research Institute, but runs Diplomas and Certificate courses.