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Food security and economic stability of many developing countries rely on the resilience of major crops to climatic variability and climatic anomalies. Since climate change forecasts predict an increasing frequency and intensity of climatic disturbances, the need to increase our knowledge about the influence of climate variability on crop productivity is especially acute for areas with fragile environments such as the semi-arid and sub-humid Chaco in South America. We used climate records from recent decades and crop growth models to: (i) identify the main climatic variables that have influenced the productivity of soybean and maize which are major crops cultivated in the area and (ii) to assess the impact of inter-annual variability of climate variables on the productivity of soybean and maize. Simulated soybean and maize grain yields indicated that farmers in Chaco should be aware of the high interannual variability in the productivity of these crops. Farmers face a different risk cropping maize and soybean depending on the location. The productivity of soybean was below production costs in 10–13% of the studied years while the corresponding values for maize were 11–14%. Diversification of crop rotations is therefore key to enhance resilience and to increase the likelihood of harnessing favorable growing conditions. Management strategies intended to conserve soil water are of paramount importance, especially for soybean where anomalies in the precipitation during the first four months after sowing was the predictor that explained the highest amount of variance in grain yield (r = 0.58). To mitigate the effect of temperature, which essentially is a factor out of direct control of the farmer, the main practice that arose from our study is delaying planting dates (e.g., towards late January) to avoid the occurrence of high temperatures during the critical stages of the crop.