Yellow fever (YF) remains a significant vector-borne zoonotic disease in tropical regions of the Americas, despite the availability of an effective vaccine for more than eight decades. In South America, the virus is maintained primarily through a jungle transmission cycle involving mosquitoes of the genera Haemagogus and Sabethes and several species of non-human primates (NHPs), which serve as amplifying hosts and important epidemiological sentinels. This narrative review revisits the current status of YF epizootics in South America and examines their implications for surveillance, ecological dynamics, and the risk of spillover to human populations. The review synthesizes recent evidence on the role of NHPs in the maintenance and detection of YF virus circulation, highlighting the high susceptibility of certain neotropical primates, particularly species of the genus Alouatta, which often experience high mortality during outbreaks. Reports of epizootics across Brazil, Colombia, Peru, Bolivia, and Venezuela illustrate the virus's ongoing circulation and geographic expansion in tropical ecosystems. Ecological factors such as deforestation, habitat fragmentation, environmental change, and increased human activity in forested areas modify transmission dynamics and increase opportunities for spillover to humans. The integration of wildlife monitoring, entomological surveillance, genomic analysis, and epidemiological data is essential to improve early detection and response. In this context, the One Health framework provides a comprehensive approach to understanding the complex interactions among humans, animals, and ecosystems that drive YF transmission. Strengthening regional surveillance systems, improving laboratory capacities, and promoting coordinated public health interventions are critical to preventing human outbreaks and mitigating the ecological and public health impact of YF in South America.