South Berwick, in southwestern York County was settled in 1624 and contains almost 14,000, mostly rural and suburban acres. Although not the location of the earliest homes, mills and farms, the densest concentration of commercial, civic and residential buildings are now found in South Berwick village proper, which is located just inland of the Salmon Falls River in the northwest corner of the town. The village developed over the course of a century and a half from 1774 through the mid-twentieth century and contains residential homes and commercial and civic buildings. The district is located along several blocks of Main Street and most of Portland Street and parts of Highland Avenue, Agamenticus Road and Academy Street, and contains 117 contributing resources and 22 non-contributing resources. It is significant in the area of transportation, as an intact late eighteenth and nineteenth century commercial and residential center which developed along an important, regional transportation corridor, known alternately as the former Dover Turnpike or the Boston-Portland Post Road. It also achieves significance under for the manner in which the settlement patterns reflect patterns of eighteenth and nineteenth century community planning and development. The district was also listed in the National Register in consideration of the architectural merit of the town's late eighteenth, nineteenth and early twentieth century businesses, residences, and civic buildings.