Characteristic of the Anthropocene, human impacts have resulted in worldwide losses in forested land cover, which can directly and indirectly drive biodiversity loss. The global illicit drug trade is one source of deforestation directly implicated with habitat loss in Central America, typically for drug trafficking and livestock production for money laundering. Given reports of deforestation in Central America linked to narcotraffic, we explored vegetation changes within Guatemala’s highly biodiverse Maya Biosphere Reserve by examining trends suggestive of deforestation in a protected area. As such, we collected satellite-derived data in the form of enhanced vegetation index (EVI), as well as history of burned areas, published human-“footprint” data, official population density, and artificial light activity in Laguna del Tigre National Park from 2002 to 2020 for descriptive analysis. We found consistent reductions in EVI and trends of anomalous losses of vegetation despite a baseline accounting for variation within the park. Analyses revealed weak correlations (R2 ≤ 0.26) between EVI losses and official sources of anthropogenic data, which may be attributable to the data’s limited spatial and temporal resolution. Alarmingly, simple analyses identified vegetation losses within a protected area, thus emphasizing the need for additional monitoring and science-based, but interdisciplinary policies to protect this biodiversity hotspot.