Large-scale transboundary conservation initiatives are necessary to respond to threats against tropical forests, and the jaguar (Panthera onca), a flagship and umbrella species in the Neotropics, is an ideal target species for such initiatives. We estimated jaguar abundance and occupancy of medium- and large-sized mammals and birds across a transboundary landscape in the northwestern Amazon biome using camera-trap data from 168 stations; specifically within three management regimes of indigenous and protected lands in Colombia (the indigenous reserve of Umancia), Ecuador (Cuyabeno Wildlife Reserve), and Peru (Güeppi-Sekime National Park). Based on spatial capture-recapture models, we estimated jaguar density in the study area at 2.20 ± 0.44 individuals per 100 km2, implying an abundance of 322 jaguars (95% CI = 217–477). These estimates suggest that an entire mega-landscape, which also includes other protected areas and indigenous lands, could harbor as many as 2000 jaguars (95% CI = 1586–3498). We found that jaguar abundance and medium-to large-sized terrestrial vertebrate species richness (totaling 24 mammals and 4 birds) were similar under the three management regimes. Overall, our study indicates that a significant healthy population of jaguars can survive in this large-scale conservation corridor that crosses country borders, a place where protected areas and indigenous territories are key. This study is among the first to take a transboundary approach for jaguar conservation in a protected but still threatened part of the Amazon biome, inhabited by several ancient indigenous people. As a large forest block, this conservation landscape serves not only as an effective buffer against deforestation and a stronghold for jaguar populations and medium- and large-sized vertebrates, but it also secures the well-being of local people.