For most of its length between its southern end in San Pedro and south of Downtown Los Angeles, it runs parallel to the west of the Harbor Freeway (I-110).

After a short distance, Normandie Avenue branches off due north while Vermont turns northeast towards its intersection with Pacific Coast Highway (PCH).

Vermont Avenue then passes at the western end of the University of Southern California and Exposition Park in South Los Angeles.

In August 2012, the City of Los Angeles designated a portion of Vermont Avenue in Pico-Union as the "El Salvador Community Corridor.

In the future, Measure M funding is expected to become available for an extension of the B Line subway down Vermont Avenue at least as far as the neighborhood of Athens (just south of the 105 Freeway), possibly as a combination of both underground and elevated heavy rail.