The people in general ought to have regard to the moral character of those whom they invest with authority either in the legislative, executive, or judicial branches.

He fought against the flood of paper money and opposed the issuance of bonds without provision for their amortization. During his two pastorates he wrote three well-known works on theology notably the satire "Ecclesiastical Characteristics" (1753) which opposed the philosophical influence of Francis Hutcheson. Witherspoon became prominent within the Church as an Evangelical opponent of the Moderate Party.

As president of the College of New Jersey (1768–94; now Princeton University) he trained many leaders of the early nation and was the only active clergyman and the only college president to sign the Declaration.