Apparent changes in vegetation distribution, fire, and other disturbance regimes throughout western North America have prompted investigations of the relative importance of human activities and climate change as potential causal mechanisms. Assessing the effects of Euro-American settlement is difficult because climate changes occur on multi-decadal to centennial time scales and require longer time perspectives than historic observations can provide. Here, we report vegetation and environmental changes over the past ~13,000 years as recorded in a sediment record from Bison Lake, a subalpine lake on a high plateau in northwestern Colorado. Results are based on multiple independent proxies, which include pollen, charcoal, and elemental geochemistry, and are compared with previously reported interpretations of hydroclimatic changes from oxygen isotope ratios. The pollen data indicate a slowly changing vegetation sequence from sagebrush steppe during the late glacial to coniferous forest through the late Holocene. The most dramatic vegetation changes of the Holocene occurred during the ‘Medieval Climate Anomaly’ (MCA) and ‘Little Ice Age’ (LIA) with rapid replacement of conifer forest by grassland followed by an equally rapid return to conifer forest. Late Holocene vegetation responses are mirrored by changes in fire, lake biological productivity, and watershed erosion. These combined records indicate that subsequent disturbance related to Euro-American settlement, although perhaps significant, had acted upon a landscape that was already responding to MCA-LIA hydroclimatic change. Results document both rapid and long-term subalpine grassland ecosystem dynamics driven by agents of change that can be anticipated in the future and simulated by ecosystem models.