Climate change, disturbance, and plant invasion threaten grassland ecosystems, but their combined and interactive effects are poorly understood. Here, we examine how the combination of disturbance and plant invasion influences the sensitivity of mixed-grass prairie to elevated carbon dioxide (eCO2 ) and warming. We established subplots of intact prairie and disturbed/invaded prairie within a free-air CO2 enrichment (to 600 ppmv) by infrared warming (+1.5°C day, 3°C night) experiment and followed plant and soil responses for 5 years. Elevated CO2 initially led to moderate increases in biomass and plant diversity in both intact and disturbed/invaded prairie, but these effects shifted due to strong eCO2 responses of the invasive forb Centaurea diffusa. In the final 3 years, biomass responses to eCO2 in disturbed/invaded prairie were 10 times as large as those in intact prairie (+186% vs. +18%), resulting in reduced rather than increased plant diversity (-17% vs. +10%). At the same time, warming interacted with disturbance/invasion and year, reducing the rate of topsoil carbon recovery following disturbance. The strength of these interactions demonstrates the need to incorporate disturbance into predictions of climate change effects. In contrast to expectations from studies in intact ecosystems, eCO2 may threaten plant diversity in ecosystems subject to soil disturbance and invasion.