Jaguars ( Panthera onca ) exert critical top-down control over large vertebrates across the Neotropics and have been declining due to multiple threats. Based on geospatial layers, we extracted socio-environmental variables for 447 protected areas across the Brazilian Amazon to identify protected areas that merit short-term high-priority efforts to maximize jaguar persistence. Data were analyzed using descriptive statistics, structural equations and regression modeling. Our results reveal that areas containing the largest jaguar densities and estimated population sizes are precisely those confronting most anthropogenic threats. We reveal that jaguars in the world’s largest tropical forest biome are threatened by deforestation associated with anthropogenic fires, and subsequent establishment of pastures. We provide a shortlist of protected areas that should be prioritized for short-term jaguar conservation. The future predicament of jaguar populations can only be ensured if protected areas can be proofed against downgrading and downsizing geopolitical pressures and external anthropogenic threats.