This article suggests the further resituating of the origins of the early European Enlightenment in what William J. Bouwsma has called the “waning Renaissance.” The waning Renaissance was more than simply a Neoplatonic reaction first against humanism and second against a moribund Aristotelianism. Instead, it bequeathed to the early Enlightenment a chastened, initially less optimistic humanism among scholars whose work prepared the way for the eighteenth-century aversion to system-building, and a greater respect for meticulously circumscribed, useful certainties. This article argues that the “waning Renaissance” derived from the increasingly pervasive perception by writers that eclectic systems fusing Hermeticism, scholasticism, and humanism represented an overweening confidence in the ability of humankind to perfect the natural and human orders. In diverse ways, this article contends that the reactions to such overconfidence by John Calvin, Francis Bacon, the Paduan Aristotelians, and Galileo foreshadowed early Enlightenment skepticism and empiricism.