AbstractWe evaluated the most relevant natural and anthropogenic factors for the occurrence and co‐occurrence of jaguars (Panthera onca) and pumas (Puma concolor) in the eastern Amazon, the most degraded portion of this tropical rainforest in Brazil. We found that in a context of high human pressure, a more significant amount of primary forest and more significant annual rainfall most positively influence the occurrence of jaguars. In contrast, pumas are negatively influenced by proximity to roads and positively by slope. Additionally, the presence of primary forest areas and high annual rainfall also favour the co‐occurrence of jaguars and pumas in the same areas. In contrast, open areas more related to anthropogenic zones disfavour the co‐occurrence of these two species in this degraded portion of the Amazon. Our results support landscape management for conserving big cat species in the Amazon and reinforce the importance of forest conservation for maintaining big cats in altered landscapes. Although these animals occur in open habitats, in the Amazon, these species are dependent on primary forests, as they are better‐structured habitats that maintain the capacity to support prey and shelter.