The Old Indian Agency House lies northeast of the downtown Portage. It was erected in 1832 for John H. Kinzie, Indian subagent to the Ho-Chunk, to serve as his home and office. The masons and carpenters were brought from St. Louis, the lumber came predominantly from Green Bay, the stone was quarried nearby, and the brick was made about two miles away on the present site of Pauquette Park. Kinzie and his wife, Juliette M. Kinzie, lived in the home until July 1833. She published a memoir, Wau-Bun: The Early Day in the Northwest, which provides an account of life in the Old Indian Agency House and at nearby Fort Winnebago. Robert McCabe, who succeeded Kinzie as Indian subagent to the Ho-Chunk, resided in the house until he resigned in July 1834. The commandant of Fort Winnebago was then appointed acting Indian subagent to the Ho-Chunk until the subagency closed in 1837. The house, left vacant after McCabe's departure, remained in federal ownership until 1854, serving a series of occupants, including a tavern (which the Fort Winnebago commandant expelled), Saterlee Clark's trading post, and a boarding house. The National Society of Colonial Dames in the State of Wisconsin acquired the house and the property on which it sits in 1931. They undertook a campaign to preserve the house, working with Madison architect Frank Riley to rehabilitate it in 1931-32.

The Old Indian Agency House is of national importance in United States history. Built in 1832, using federal funds, to serve as the home and office of the Indian subagent to the Ho-Chunk, a use it served until July 1834, this property represents a pivotal moment in the evolution of federal Indian policy. Federal Indian policy was closely intertwined with the settlement and westward expansion of the United States. This pivotal moment is the brief period between about 1817 and 1834, when the federal government struggled to choose between two opposing approaches to Indian policy: to "civilize" Indian people, that is, of adopting Euro-American agricultural, economic and societal practices, and assimilating into Euro-American society as the nation expanded westward; or to view Indian tribes as an impediment to Euro-American settlement, and remove them west of the Mississippi River. The critical period of this debate took place during the administration of Andrew Jackson, 1829-1837. At the beginning of his administration, public opinion had moved in the direction of removal, the principal issue on which Jackson had campaigned. By the end of Jackson's administration, 46,000 Indian people had been relocated to the west. The Old Indian Agency House represents the "civilize and assimilate" approach to federal Indian policy, and its construction and use coincides with the most intense time in the debate over federal Indian policy.

The Old Indian Agency House is open seasonally for tours.

Additional documentation and a boundary increase approved for the State Register on August 19, 2011, and for the National Register on June 20, 2012. The boundary increase has NRIS number 12000353.