We present a theory of the origins and enforcement of the nuclear nonproliferation regime based on a game-theoretic model of proliferation. The theory synthesizes the popular, but incomplete, views of the regime as a grand bargain or a cartel. Widespread nonproliferation is only possible if the superpowers collude to coerce some states into compliance, as in the cartel, but this enforcement is only affordable if most states voluntarily comply under a grand bargain. This collusion arises from the superpowers’ early experience of proliferation and its disruptive effects on intra-alliance politics. We document collusion in the negotiation and enforcement of the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) and find support for the theory’s predictions in a data set of superpower reactions to states’ failure to join or comply with the NPT. Our theory implies that the regime has substantially reduced proliferation, in contrast to previous studies’ findings.