He ran unsuccessfully for Governor of Massachusetts three times (1820–22), losing each time to the popular moderate Federalist John Brooks. In 1823 Eustis won the seat in a highly contentious contest with the unpopular arch-Federalist Harrison Gray Otis. Republicans presented Eustis as a moderate successor to Brooks who would be less partisan than Otis, and also highlighted his Revolutionary War experience. He carried Federalist strongholds in Hampshire and Essex Counties, and very nearly defeated in Otis in Boston. Eustis' victory in the election (combined with a Republican sweep of the legislature the following year) marked the effective end of the Federalist Party in Massachusetts.