Prehistoric and early historic human cultures are known to be closely connected to and dependent on their natural environments. We test the hypothesis that climate change influenced the means of subsistence of ancient tribes and favored agricultural or cattle herding economic strategies. Our study area is the Khakass–Minusinsk Hollow, located in the foothills of the Sayan Mountains, south-central Siberia, which was, for a few millennia, a buffer zone for human migrations across the Great Eurasian Steppe. Three different methods (the Montane BioClimatic Model, MontBCliM; the biomization method; and the actualizm method) are employed to reconstruct vegetation taken from the fossil pollen of sediment cores in two mountain lakes at eleven time slices related to successive human cultures back to the mid-Holocene. MontBCliM model is used inversely to convert site paleo-vegetation into site paleo-climates. Climate-based regression models are developed and applied to reconstructed climates to evaluate possible pasture and grain crops for these time slices. Pollen-based reconstructions of the climate fluctuations uncovered several dry periods with steppe and forest-steppe and wetter periods with forests since 6000 BP. Grasslands increased by an order of magnitude during the dry periods and provided extensive open space suitable for pastoralism; however, both grain and pasture yields decreased during these dry periods. During wetter climates, both grain and pasture yields increased twofold and supported more fixed human settlements centered around farming and cattle herding. Thus, the dry periods favored pastoralist rather than farming activities. Conversely, tribes that practiced agriculture had some advantage in the wet periods.