A simple quantitative approach is presented for determining the relative importance of climate change and human impact in driving late Quaternary megafaunal extinctions. This method is designed to determine whether climate change or human impact alone can account for these extinctions, or whether both were important, acting independently (additively) and/or synergistically (multiplicatively). This approach is applied to the megafaunal extinction in the Última Esperanza region of southern Chile. In this region, there is a complex pattern of extinction. Records of environmental change include temperature proxies and pollen records that capture the transition from cold grasslands to warmer, moister forests, as well as evidence of initial human arrival. Uncertainty in extinction times and time of human arrival complicates the analysis, as does uncertainty about the size of local human populations, and the nature, strength, and persistence of their impacts through the late Pleistocene and early Holocene. Results of the Ultima Esperanza analysis were equivocal, with evidence for climate- and human-driven extinction, with each operating alone or additively. The results depend on the exact timing of extinctions and human arrival, and assumptions about the kinds of pressures humans put on the megafauna. There was little evidence for positive synergistic effects, while the unexpected possibility of negative synergistic interactions arose in some scenarios. Application of this quantitative approach highlights the need for higher precision dating of the extinctions and human arrival, and provides a platform for sharpening our understanding of these megafaunal extinctions.