The late Quaternary was a time of considerable environmental change in North America. Not only was climate highly variable, but a megafaunal extinction at the terminal Pleistocene led to considerable loss of biodiversity. These combined perturbations likely had cascading effects across communities and ecosystems. Here, we focus on a detailed fossil record on the Edwards Plateau in Texas and the response of Neotoma, a genus of herbivorous rodents, to these environmental and ecological perturbations. We characterized changes in Neotoma body mass and diet across the past 20,000 years; body mass was estimated using measurements of fossil teeth and diet quantified using stable isotope analysis of carbon and nitrogen isotope from fossil bone collagen. We found that prior to ~7,000 cal yr BP, maximum mass was positively and significantly correlated to precipitation and negatively correlated to temperature. Independently, body mass was significantly and negatively correlated to communtiy composition becoming more similar to modern over time. Moreover, while Neotoma diet in the Pleistocene was primarily sourced from C₃ resources, it became progressively more reliant on C₄ (and potentially CAM) plants through the Holocene. The combination of decreasing population body mass and higher C₄/CAM consumption was associated with a regional transition from a mesic forest to a xeric savanna grassland. Our results suggest that Neotoma during the terminal Pleistocene were responding to climatic factors through changes in body size, while changes in local resource availability during the Holocene likely led to changes in the relative abundance of different Neotoma species in the community.