The Bethune-Thompson House in Williamstown owes its name to two prominent owners — the Reverend John Bethune and explorer David Thompson. But it was Peter Ferguson, an early settler, who first built a house on this site in 1784. Its walls were constructed using the French-Canadian "poteaux sur sol" technique, which placed logs in vertical rows held together top and bottom by horizontal plates. Reverend John Bethune (1751-1815), the minister of St. Andrew's Presbyterian Church in Williamstown and the first Presbyterian minister in Upper Canada, acquired the property in 1804. He built a larger house which incorporated Ferguson's home as its kitchen wing. In 1815, the house was acquired by David Thompson (1770-1857), the famous North West Company explorer who mapped much of what is now western Canada.

The Ontario Heritage Trust acquired Bethune-Thompson House in 1977. (Eleven years later, the Trust bought the adjacent worker's cottage, a timber-framed structure from the early 1840s.) The Trust's conservation strategy for Bethune-Thompson House integrated various heritage disciplines to provide a comprehensive approach to recording and restoring the site. Extensive archaeological, architectural and historical research was conducted before the property was restored between 1985 and 1987. The Bethune-Thompson project became a model that the Trust followed in subsequent restorations of its properties.

The Bethune-Thompson House — a National Historic House — is the oldest residence owned by the Trust.