The Mary Worthington Macomb House is a historic residence in southern Chillicothe, Ohio, United States.

One of the oldest buildings still in existence in Chillicothe, the Macomb House sits on a land tract of 35 acres (14 ha) that was originally owned by Nathaniel Massie.

[3] Although Mary and her family lived in the grand Adena Mansion on Chillicothe's northern side,[4] she chose to marry lower in society circa 1816.

Her new husband, David Macomb, was a member of a prominent local family, but his poor management of their property forced them into debt, and they settled in the southern United States, where Mary died while moving to Texas in 1836.

[3] Before moving southward, the Macombs resided in the present two-story house, which is built primarily of large blocks of sandstone.