Main Street Station began its life as Richmond’s official train station more than a century ago in 1901. By the mid-20th century, however, area floods, the demise of the Shockoe Bottom district, the increasing popularity of air and auto travel, and the presence of the much-larger Broad Street Station (now the Science Museum of Virginia) led to the station’s demise. Even after receiving recognition as a state and national historic landmark in 1970, the station could not survive. This demise was further compounded by the flood associated with Hurricane Agnes in 1972, when the waters of the nearby James River flooded the station’s first floor. Following the last train service to the station in 1975, to further exacerbate any future the station had, a fire damaged the station in 1976. The station saw a hint of renewal in 1985 when a shopping mall opened in the train shed behind it. Flooding and economic hard times befell this venture, however, and the mall ceased operations two years later. In the early 1990s the shed became home to state health offices for 650 employees.

With the prospects of multimodal transportation in Richmond's future, the City renovated and reopened Main Street Station to Amtrak service in 2003. Even with the protection of the City's floodwall, Shockoe Bottom was flooded again in 2004 by Tropical Storm Gaston.

Today, Main Street Station continues to serve Amtrak travelers and serves as a popular venue for wedding receptions, private functions and corporate events.