North American bison undergo a dramatic decrease in body size during the Late Quaternary. While a change in size has long been recognized, the rate and timing of diminution recently has become defined better for Southern Plains bison. Questions regarding what force drove the decrease in body size, however, continue to generate new hypotheses and the use of novel methodological approaches. While many variables influence body size, morphological changes in bison historically are attributed to either human hunting or climate change. New data from a sample of metapodials from well-dated Southern Plains localities depict a rapid decrease in body size in the early Holocene with modern size present by 6500 BP. The pattern and rate of evolution on the Southern Plains is compared to existing hypotheses for bison diminution over the Late Quaternary. Bison size on the Southern Plains correlates best with the spread of the C4 ecosystem between ca. 8000 and 6500 BP. C4 grasses are less nutritious than the C3 grasses they replaced and this decrease in nutritional value of the bison's primary food source likely led to the decrease in body size. The properties of C4 grasses adequately account for the size reduction of Late Quaternary bison.