The main campus of Our Lady of Fatima University is located in Valenzuela City, on the outskirts of Metropolitan Manila. Highly charged and steaming with activities, the main campus houses the College of Medicine Building and the St. Martin de Porres Building where the College of Dentistry and College of Business and Accountancy are situated.

The range of foreign students expose the learners to diverse cultures and likewise gives the community an international touch. Valenzuela Campus has easy access to downtown Manila and metro Quezon City. Bus and taxi commutes are easy and numerous. The metro train terminals (Light Railway Transit: Northwest to Southwest and Metro Rail Transit: North to South) are only 15 to 25 minutes ride away from the campus.

The Valenzuela City Campus also exclusively houses the College of Medicine, College of Dentistry, and College of Maritime Education.