Aquifer depletion poses a major threat to the ability of farmers, food supply chains, and rural economies globally to use groundwater as a means of adapting to climate variability and change. Empirical research has demonstrated the large differences in drought risk exposure that exist between rainfed and irrigated croplands, but previous work commonly assumes water supply for the latter is unconstrained. In this paper, we evaluate how aquifer depletion affects the resilience of irrigated crop production to drought risk using over 30 years of data on historical corn and soybean yields, production areas, and aquifer conditions for the High Plains region in the United States. We show that aquifer depletion reduces the ability of farmers to sustain irrigated crop yields and production areas in drought years. Our findings demonstrate that drought-related production losses on irrigated croplands increase non-linearly with aquifer depletion, highlighting the need for proactive aquifer conservation interventions to support adaptation and resilience to future increases in rainfall variability under climate change.