Protected areas (PAs) are important mechanisms for conserving biodiversity and buffering anthropogenic pressures, but the expansion and intensification of human activities within and around PAs are threatening the biological diversity they are designed to protect. In South America, a region which includes many biodiversity hotspots (e.g., Atlantic Forest, Andes), agriculture, mining, oil and gas exploitation, dam construction, and settlements have been expanding and intensifying within and around PAs. These human activities need infrastructure (e.g., buildings, logistic facilities, ports), which leads to increased pressure on PAs. In this study, we used nighttime light data and the World Database on Protected Areas to evaluate the extent of intrusion of infrastructure in PAs in South America between 2001 and 2011. Our results show that in general PAs in all of the seven IUCN categories are buffering the intrusion of infrastructure within them, but this was not the case for PAs in multiple-use categories where there was a considerable increase in infrastructure within these PAs. The largest increase in infrastructure occurred within the first 60 km from the border of the PAs, and for multiple-use categories, the peak occurred in the first 10 km. In addition, infrastructure expansion around PAs in category I showed more variability and the largest extent. Infrastructure expansion within and around PAs varied among countries. There were only 23 of the 2,902 PAs with zero expansion, 16 were located in Brazil, four in Colombia, and one in Suriname, Venezuela, and French Guiana. Ecuador and Venezuela were the two countries that had the most infrastructure expansion within and around their PAs, while Guyana and French Guiana had the least development. Presently, South America has ∼22% of the land area under some type of protection. Hopefully, the management of PAs will improve to help buffer the impacts of human activities and improve biodiversity conservation. Unfortunately, our results show that opposite, infrastructure is expanding within and around the PAs, which will most likely lead to ecological degradation and isolation of many of these PAs.