Introduction: Human–animal contact (HAC) is a key driver of zoonotic disease emergence and transmission, yet population-based data from Latin America remain limited. The objective of this study was to characterize HAC patterns and estimate zoonotic exposure in wildlife-rich settings across Bolivia, Chile, and Guatemala. Methods: A cross-sectional Knowledge, Attitudes, and Practices survey was conducted among 2,389 participants in rural, urban, and protected areas to collect direct, indirect, and foodborne contact with domestic and wild animals. Frequencies and patterns of HAC were analyzed and visualized using heatmaps, and a Zoonotic Exposure Index was developed based on literature-derived weightings for rabies, brucellosis, and bovine tuberculosis. Group differences were analyzed according to sociodemographic and knowledge-related factors. Results: Overall, 92% of participants reported domestic animal contact—most frequently with dogs, cats, poultry, and swine—while 32% reported wild animal contact, predominantly with wild birds, rodents, and bats. 99% of individuals with wildlife contact also reported contact with domestic animals. Direct interactions, including ownership, handling, and slaughtering, were most common, whereas indirect and foodborne contacts were less frequent. Adolescents showed the highest exposure. Higher education, income, and prior training on zoonoses were associated with lower exposure. Conclusion: The study confirms the widespread nature of HAC across wildlife, livestock, and humans. The zoonotic Exposure Index offers a useful framework, and exposure estimates provide baseline data to support pathogen surveillance and predictive risk modeling in the region. Adolescents and low-income populations emerge as key targets for One Health interventions.