Purpose Rising corn prices in the USA due partly to increasing ethanol demands have led to a significant expansion of corn areas displacing natural vegetation and crops including cotton. From 2005 to 2009, cotton area harvested in the USA nearly halved with a reduction of 2.5 million hectares, while that of corn increased by 1.8 million hectares. However, environmental impacts of land shifts from cotton and corn have been largely neglected in literature. Methods In this study, we evaluate the environmental properties of US corn and cotton production and implications of land cover change from cotton to corn using state-specific data and life cycle impact assessment. Focusing on regional environmental issues, we cover both on-farm direct emissions such as different types of volatile organic compounds and pesticides and indirect emissions embodied in input materials such as fertilizers. TRACI 2.0 is used to evaluate the environmental impacts of these emissions. Results and discussion The results show that US cotton and corn productions per hectare on average generate roughly similar impacts for most impact categories such as eutrophication and smog formation. For water use and freshwater ecotoxicity, corn shows a smaller impact. When land shifts from cotton to corn in cotton-growing states, however, the process may aggravate most of the regional environmental impacts while relieving freshwater ecotoxicity impact. The differences in the two estimates are due mainly to underlying regional disparities in crop suitability that affects input structure and environmental emissions. Conclusions Our results highlight the importance of potential, unintended environmental impacts that cannot be adequately captured when average data are employed. Understanding the actual mechanisms under which certain policy induces marginal changes at a regional and local level is crucial for evaluating its net impact. Further, our study calls for an attention to biofuel-induced land cover change between crops and associated regional environmental impacts.