CONTEXTFarmers in the federal state of Mato Grosso contribute about one-third of national grain production in Brazil. Given their key role in providing food and feed for fast-growing world demand, major shocks on Mato Grosso's farm holdings can lead to devastating consequences for vulnerable consumers and producers inside and outside Brazil. Research has shown that rising temperature and water stress threaten the agricultural productivity of Mato Grosso's rain-fed farm production systems. Failure of current production systems on existing croplands may also foster agricultural expansion and increase pressure on the remaining native forest. Balancing agricultural production and environmental protection is of particular concern in Mato Grosso because more than half of its territory is in the Amazon Rainforest biome. The tight schedule of field activities within double-cropping systems reduces farmers' ability to adapt to climate change and manage shocks. The increasing uncertainty about climate change and price volatility further complicate farmers' decision-making. OBJECTIVEThis study evaluates the impact of two climate change scenarios on the profitability of double-cropping systems, considering not only climate variability but also economic uncertainties faced at the farm level. METHODSOur modeling system combines future climate projections with biophysical and bioeconomic models. We used high-performance computing with many compute nodes and large shared memory to account for the large heterogeneity of possible management options and farm-gate prices. RESULTS AND CONCLUSIONSSimulation results indicate that farmers in Mato Grosso could be exposed to significantly lower economic returns, with a future gross margin reduction of 69% on average compared to current levels. Moreover, the number of profitable cropping alternatives could drop by 18% on average. According to our simulations, climate impacts on gross margins are likely to differ in Mato Grosso, with the Southeast macro-region being the most affected and the South Central region the least. The simulation results also revealed a higher risk of losses during the second cropping season. Double-cropping systems with cotton were the most impacted by changing climatic conditions, and sunflower the least. SIGNIFICANCEThis study revealed that climate change might negatively affect double-cropping systems in the Southern Amazon due to reduced annual precipitation, a shortening of the rainy season, and shifts in the rainy season's onset and cessation dates. Our bioeconomic simulations further suggest that farmers in Mato Grosso could lose one of their most significant comparative advantages, namely the possibility of harvesting two crops in one cropping season.