The Pantanal wetland harbours the second largest population of jaguars in the world. Alongside climate and land-use changes, the recent mega-fires in the Pantanal may pose a new threat to the jaguars’ long-term survival. To put these growing threats into perspective, we addressed the reach and intensity of fires that have affected jaguar conservation in the Pantanal ecoregion over the last 16 years. The 2020 fires were the most severe in the annual series, followed by 2019, burned 31% of the Pantanal and affected (I) 45% of the estimated jaguar population (87% of these affected in Brazil); II) 79% of the home range (HRs) areas, and (III) 54% of the protected areas (PAs) within HRs. Fires consumed core habitats and injured several individual jaguars, the Pantanal’s apex predator and umbrella species. Displacement, hunger, dehydration, territorial defence, and lower fecundity are among the impacts that may affect the abundance of the species. These impacts are likely to affect other less mobile species and, therefore, the ecological stability of the region. A solution to prevent the recurrence of mega-fires lies in combating the anthropogenic causes that intensify drought conditions, such as implementing actions to protect springs, increasing the number and area of PAs, regulating the use of fire, and allocating fire brigades before dry seasons.