De La Salle University occupies a 5.04 hectare lot along busy Taft Avenue in Manila. It is about four kilometers away from Manila's City Hall and is easily accessible by public transportation. Along this kilometer radius are situated other colleges and universities, a sports center complex, the Bangko Sentral ng Pilipinas, the Cultural Center of the Philippines complex, a row of four-and-five-star hotels, restaurants, shopping and entertainment centers, as well as main feeder roads. The rest of Metropolitan Manila and its environs are easily accessible by private or public transportation.
The University is also served by Manila's Light Rail Transit (LRT) which hastens the travel time of commuters. The proximity of the LRT stations (Pablo Ocampo Avenue [formerly known as Vito Cruz Ave.] - Quirino Avenue) to the University facilitates traveling via LRT.