A Harvard graduate and typical member of a New England upper class family, Winthrop distinguished himself by gaining knowledge of the Northwest Territory as a surveyor. This led to his appointment as the first Secretary of the newly created Northwest Territory Government, and his eventual tenure as Acting Governor of the region.

His job was to organize and enforce government and law and order in the frontier territory, and his unbending principles played a major role in achieving these goals. He also served as Governor of the Mississippi Territory, helping to tame and organize that area.