In 1655, a handful of land-speculating colonists orchestrated the purchase of the Setauket area from the local natives. The region's first European settlers were English migrants from New England. This was the first settlement in what later became the Town of Brookhaven, and both the hamlet and town use the 1655 date as their origin. During the 17th century, Setauket was synonymous with the colonial town of Brookhaven.
During the 1660s the settlement was temporarily renamed Ashford. This change was facilitated by Captain John Scott, a professional mercenary hired to clear out the Native American Indians, an early settler of Setauket and an important leader in Long Island's early history who briefly served under the title of President of Long Island. A crafty land speculator, Scott claimed at one point to own a third of the island including the Setauket area. Despite the questionable nature of many of his claims, John Scott had enough power and support to rename Setauket for his ancestral homeland in England, Ashford, Kent, and to construct a stately home named Egerton.
Setauket has a New England–style village green with a mill pond and park, a small post office, the Caroline Church built in 1729, and the Setauket Presbyterian Church established in 1660. The Emma S. Clark Library, also on the Village Green, is often considered one of the most comprehensive on Long Island. This section is the historical center of the original settlement and forms the core of the Old Setauket Historic District. The mill pond is additionally within the public Frank Melville Memorial Park.
Almost all of the commercial establishments in Setauket are concentrated in three areas: on Route 25A (here also known as North Country Road), Belle Meade Road (formerly called Terminal Road after the oil terminal), and on New York State Route 347/Nesconset Highway. Numerous medical and professional offices are located on Belle Meade Road, along with other businesses that service them. A few additional shops and factories were established before modern zoning rules went into effect, a handful of which are located on Gnarled Hollow Road and Comsewogue Road. The remainder of Setauket is predominantly residential.
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