Large closed basins are often associated with regions of active tectonics. In contrast, we provide the example of the Great Divide Basin, in southern Wyoming, where climate change, through its impact on erosion and flexure, provides the primary mechanism of basin closure. Two- and three-dimensional flexural models that incorporate the effects of local basin abandonment due to aridity as well as minor extrabasinal extension demonstrate that basin closure with 40 m of basement relief (tilt) could have been achieved in the Great Divide Basin under reasonable assumptions of sediment rock density and flexural rigidity. The primary drive for basin abandonment was insufficient discharge that retarded river downcutting. Continued erosion in the surrounding drainage led to flexural rebound, against which erosion by the outlet from the Great Divide Basin was unable to compete. Eventually, the basin became detached and isolated from the surrounding drainage, and a few tens of meters of differential tilt developed between the basin floor and spillover point. An extra amount of tilt, up to a few meters, could have been attained by rift shoulder effects associated with minor nearby extension outside of the basin to the north. Hence, closure of the Great Divide Basin took place with no internal faulting, nor did it require any extrabasinal tectonic activity to force basin closure. Hence, basin closure and/or drainage reorganization need not record tectonic activity in all cases. Differential erosion provides an alternative hypothesis that does not reflect local tectonic timing. Our model of the evolution of the Great Divide Basin illustrates a mechanism by which basins can become closed by climatic effects alone.