The Southern Railway Depot, also known as the North Wilkesboro Depot, is located along Cherry Street, CBD Loop and Ninth Street.
It was built in 1914 by the Southern Railway, and is a long, one-story brick building with American Craftsman style design elements. It measures 36 feet wide and 240 feet long and has a low hipped roof with overhanging eaves. Passenger service ceased in 1955.
It was listed on the National Register of Historic Places on September 10, 2004.