Upon his return from Europe, Eustis purchased the mansion in Roxbury built by royal governor William Shirley in the 1750s (which is now known as the Shirley-Eustis House). Eustis was again elected to Congress in a special election called after the resignation of Representative Edward Dowse. He served from 1820 to 1823, presiding as chairman of the U.S. House Committee on Military Affairs. In the debate on the admission of Missouri as a state (leading to the Missouri Compromise), Eustis made an impassioned speech in opposition to proposed language in the Missouri Constitution forbidding the entry of free blacks into the state.