Thomas Jefferson's brother-in-law Francis Eppes built this frame house and in true Jeffersonian fashion it took many years. Eppes began construction around 1770 but did not complete the house until a few years before his death in 1808. Much of the time, he and his family lived in what could only have been a construction site with innumerable changes being made throughout the decades. When widower Jefferson prepared to go to Paris in 1782 as minister to France, he sent his two youngest daughters to join the Eppes family. Two years later, Lucy, his youngest, died and was buried at Eppington. Returning from Paris in 1789, Jefferson was at Eppington when he received the letter from President George Washington appointing him secretary of state. Further strengthening the connection between the two families, Jefferson's daughter Maria married Francis Eppes's son John Wayles Eppes in 1797 and lived at Eppington much of the time until her death in 1804.
Eventually, Francis Eppes settled on the house's present three-part layout, an arrangement that was becoming fashionable in Southside at the end of the eighteenth century. The late-eighteenth-century Belnemus (PO7) in neighboring Powhatan County closely resembles Eppington. Eppes eventually devised what was essentially a divided lateral passage in front of the two large rooms of the central block. He created a clear division inside with public spaces on one side and private rooms on the other. He also added dormers and trimmed out the attic. Jefferson tried unsuccessfully to persuade Eppes to make further changes, including a colonnade and an octagon. Except for rebuilding the front and rear porches in the third quarter of the nineteenth century and adding a rear wing (c. 1910), the character of the house has changed little since Eppes's death in 1808.