In the Midwest, agriculture is a $200 billion industry and represents one of the most intensive agricultural areas in the world. In spite of the nickname, “Corn Belt,” 25% of the Midwest’s arable land produces crops other than corn and soybean. Favorable climate and superb soil resources make this region an agricultural hot spot. However, climate change and intensive farming practices threaten the sustainability of Midwestern agriculture. Can farmers cope with increasingly heavy rainfall, rising temperatures, and increased risk of pest outbreaks? Here, we discuss ongoing climate related challenges facing Midwestern agriculture and conclude with an overview of adaptation strategies.