On November 20, 1824, over 403 acres of land was turned over to a bank in Lancaster by a farmer. The bank sold 165 acres and 68 square perches of that land, on January 29, 1828 to William Jenkins. Jenkins had a house constructed on the property and named it "The Wheatlands", either after the surrounding wheatfields or because the site of the house used to be a wheatfield. In 1845 William M. Meredith bought the house and primarily used it as a summer house.

Wheatland was put up for sale by Meredith and was contacted in June 1848 by Secretary of State James Buchanan, who was interested in the house. Buchanan moved into the mansion several months later. Buchanan ran unsuccessfully for the Democratic Party's nomination for President in the 1852 election, however he was appointed the Minister to Great Britain by the newly elected Franklin Pierce. Buchanan did not return to the United States, and to Wheatland, until 1856.

Not long after arriving back at Wheatland, Buchanan was nominated by the Democratic Party to be its candidate for President on June 9, 1856. Buchanan conducted his campaign from Wheatland as a "front porch campaign".