Over the last few years, understanding of the effects of increasingly interconnected global flows of agricultural commodities on coupled human and natural systems has significantly improved. However, many important factors in environmental change that are influenced by these commodity flows are still not well understood. Here, we present an empirical spatial modelling approach to assess how changes in forest cover are influenced by trade destination. Using data for soybean-producing municipalities in the state of Mato Grosso, Brazil, between 2004 and 2017, we evaluated the relationships between forest cover change and the annual soybean trade destination. Results show that although most of the soybean produced in Mato Grosso during the study period (60%) was destined for international markets, municipalities with greater and more consistent soybean production not destined for international markets during the study period were more strongly associated with deforestation. In these municipalities, soybean production was also significantly correlated with cattle and pasture expansion. These results have important implications for the sustainable management of natural resources in the face of an increasingly interconnected world, while also helping to identify the most suitable locations for implementing policies to reduce deforestation risks.