When it was built, the house was aligned with the Old Coach Road which once ran between Richmond and Appomattox; archaeological evidence of the roadbed has been uncovered not far from the property.

It was evidently constructed sometime before 1794, as Francisco took up residence in the house in that year, living there until the mid-1820s (one source[4] states that he took possession in 1785, while another [6] suggests, on the basis of style, a date between 1790 and 1810).

Francisco himself had local ties, having grown up at Hunting Towers, the nearby estate of Patrick Henry's uncle Judge Anthony Winston.

[3] It is unknown how he came to own the land upon which Locust Grove sits; family tradition holds that he received it from local planter James Anderson, who had been the father of his first wife, Susannah.

She persuaded him to leave the countryside for a more comfortable life in Richmond, where he worked as the Serjeant-at-Arms of the Senate of Virginia, and in which city he remained until his death.

[6] Peter Francisco died in 1831; after him, the next recorded tenant of Locust Grove was one Robert Rives, who owned it for a brief time in 1845.

[4] The Society of the Descendants of Peter Francisco took charge of the land beginning in the early 1970s, leasing it from its owners at the rate of one dollar a year.

The intent was to restore the house and turn it into a museum and shrine dedicated to Francisco's memory; while the restoration was completed, due in part to matching funds granted by the United States government upon conferral of the National Register listing, the museum was never created, and the house reverted to private ownership.

A collection of papers related to the history of Locust Grove is part of the archive of the Society of the Descendants of Peter Francisco held at the Library of Virginia.

[7] As part of the restoration work done on Locust Grove in the late 1980s, students from Longwood College visited the home and grounds and conducted an archaeological dig which covered various portions of the property.