It was in this area that historic old Fort Winnebago, one of a chain of forts along the Fox-Wisconsin Waterway, was in use from 1828 to 1853. It is situated on the head of the Fox River and is the beginning of the Portage that links Lake Michigan, through the Fox River with the Wisconsin River, which empties into the Mississippi. In this area also the French exploring party headed by Louis Joliet and Jesuit missionary, Father Jacques Marquette, portaged from the Fox to the Wisconsin in 1673, thus opening the route used by French, British, and American fur traders for more than a century.

Surgeon Lyman Foote arrived at Fort Winnebago in 1834. He was probably the first doctor to occupy the house; his predecessors had been quartered in the Fort itself. After Foote's five-year tenure, the Surgeons' Quarters became the home of Surgeon C. H. Laub, who remained until the last garrison left in 1845.

The building and property were ordered sold in December 1853. Jefferson Davis, who had been a young lieutenant in the first garrison, was Secretary of War at the time.