The former Port Melbourne Railway Station building is historically significant by association with the first public steam railway in Australia, and with the development and use of the Port Melbourne piers. The building played an important role in the history of the piers, in particular Station Pier, and in the social history of Melbourne through its association with the popular bay excursion trade.
The former Port Melbourne Railway Station building, which was rebuilt at a time when the function of the piers was expanding, is significant in demonstrating a critical change in the maritime activity of the Bayside area. Its significance is further enhanced by the fact that, unlike the piers, it has not been dramatically altered throughout the twentieth century.
The former Port Melbourne Railway Station building is of architectural and historical significance as a distinctive building type, that only representation within the metropolitan context of a small group of station buildings developed by the Victorian Railways Department following the 1890s depression. This significance is enhanced by the integrity of its building fabric.