The James S. Hamilton House is located at 150 South Milledge Avenue (Tax Parcel No. 12-2-B4-J-004).
 

Bearing the mixed influence of Federal, Greek Revival, and Italianate styles, this two-story dwelling was built on the familiar four-over-four room, central hall plan. A one-story cast-iron porch and balustrade give distinction to the stuccoed brick exterior. The elaborate grillwork utilizes a combination of Gothic, Classical, and Byzantine motifs. Stone lintels cap the triple-hung first-floor windows and the main entrance, which is framed by a transom and sidelights and crowned by a second-story Palladian style window. Massive Italianate brackets with pendant drops call attention to the wide eaves. Although the property once included a detached kitchen, smoke house, servants' quarters, corn crib, carriage house and stables, none of these outbuildings remain. A dormitory addition extends from the rear of the building.

In 1857 Dr. James Sherwood Hamilton purchased two lots on South Milledge Avenue from the university trustees and chose Athens architect Ross Crane to build this residence. Although construction began in 1857, the ornamental ironwork from the Wood-Perot Foundry in Philadelphia was not added until 1861. Dr. Hamilton served as the director of several railroads, trustee of the University of Georgia, and president of the Princeton Manufacturing Company. Hamilton died in 1888; following the death of his wife in 1896, the will was contested, resulting in a law suit that eventually forced the five Hamilton sisters to purchase their family home at sheriff's auction in 1900. Financial difficulties prompted the sale of the property around 1906-07 to Edward Hodgson III, president of the Empire State Chemical Company. The Hodgsons refurbished the home, installed water and electricity as well as the granite stairs, and demolished the neglected outbuildings. Alpha Delta Pi Sorority acquired the property from the Hodgsons in 1939, completed restoration efforts, and added the rear dormitory wing.

The James S. Hamilton House is listed on the National Register of Historic Places (April 24, 1979) and has been locally designated as a Historic Landmark (March 6, 1990).