||The built environment, defined as all human-made infrastructure, is increasing to fulfill the demand for human settlements, productive systems, mining, and industries. Due to the profound direct and indirect impacts that the built environment produces on natural ecosystems, it is considered a major driver of land change and biodiversity loss, and a major component of global environmental change. In South America, a global producer of minerals and agricultural commodities, and a region with many biodiversity hotspots, infrastructure expanded considerably between 2001 and 2011. This expansion occurred mainly in rural areas, towns, and sprawling suburban areas that were not previously developed. Herein, we characterized the areas of major infrastructure expansion between 2001 and 2011 in South America. We used nighttime light data, land use maps, and socio-economic and environmental variables to answer the following questions: (1) Where are the hotspots of infrastructure expansion located? and (2) What combination of socio-economic and environmental variables are associated with infrastructure expansion? Hotspots of infrastructure expansion encompass 70% (337,310 km2) of the total infrastructure expansion occurring between 2001 and 2011 across South America. Urban population and economic growth, mean elevation, and mean road density were the main variables associated with the hotspots, grouping them into eight clusters. Furthermore, within the hotspots, woody vegetation increased around various urban centers, and several areas showed a large increase in agriculture. Investments in large scale infrastructure projects, and the expansion and intensification of productive systems (e.g., agriculture and meat production) play a dominant role in the increase of infrastructure across South America. We expect that under the current trends of globalization and land changes, infrastructure will continue increasing and expanding into no-development areas and remote places. Therefore, to fully understand the direct and indirect impacts of land use change in natural ecosystems studies of infrastructure need to expand to areas beyond cities. This will provide better land management alternatives for the conservation of biodiversity as well as peri-urban areas across South America.