John Lawson visited Salmon Creek prior to 1710 and described the then-existing structure as "a log house such as the Swedes in America very often make, and are very strong." The area had been designated by the Lords Proprietors in 1676 as a site for one of three towns they wished to be established "where the shipps shall lade and unlaid." In the 1680s and 1690s Proprietor Seth Sothel, perhaps with that end in mind, built a considerable establishment at the site with a two-story manor house, ship's landing, dairy house, and stock of cattle. Throughout most of the eighteenth century it was owned by William Dukinfield and his descendants. At Dukinfield's death in 1721 the property went to his nephew, Nathaniel Dukinfield, who also later inherited the baronetcy of his father, Sir Robert Dukinfield. The Dukinfields built a gristmill on Salmon Creek by 1721 and a "pitch landing" for the naval stores business by 1738. Governors Edward Hyde and Thomas Pollock also lived at the site, and the main engagement of the Cary Rebellion was fought at the creek's mouth in June 1711.
Salmon Creek was the principal setting for George Higby Throop's novel, Bertie; or, Life in the Old Field (1851). The Capehart family operated a highly successful herring fishery at Avoca, with its plantation on Salmon Creek, during most of the nineteenth century and into the twentieth century.