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Livestock predation constitutes the primary source of conflict between humans and large carnivores. Moreover, human factors, such as attitudes and emotions, can affect people's tolerance towards carnivores, exacerbating the conflict. Such conflicts often lead to retaliatory killing of carnivores, which not only poses significant threats to species conservation but also to ecosystem functioning and services. Therefore, mitigating human-carnivore conflicts is essential to promote both species conservation and human well-being. Here, we studied the conflict between extensive cattle ranching and the conservation of jaguars (Panthera onca) and pumas (Puma concolor) in 129 ranches located in the Amazon arc of deforestation. We interviewed ranchers about livestock management procedures, livestock mortality, approaches to reduce predation in the area, and attitudes regarding carnivores and conservation. Our results revealed that ranchers did not perceive carnivore attacks as the primary cause of cattle mortality. However, they exhibited a significant lack of tolerance towards these incidents, partially explained by economic reasons. They also showed negative attitudes towards big cats, which were mainly associated with social factors, such as low educational background. As a consequence, jaguar and puma were frequently killed in retaliation. Ranches showed different vulnerability to attacks depending on cattle management (cattle density, calves) and landscape (forest cover inside the ranch, distance to national parks). Our findings suggest that the conflict between cattle ranching and big cats conservation in the Amazon deforestation frontier is trigger by livestock predation, but perpetuated by limited knowledge about carnivores, the lack of support from the government to mitigate livestock losses, and the perception that conservation laws conditioned the viability of cattle ranching. Forthcoming mitigation strategies should focus on interventions designed to increase people's tolerance towards jaguars and pumas (e.g. improving knowledge about ecosystem services provided by large carnivores). [ABSTRACT FROM AUTHOR]