Background: One Welfare expands the One Health approach by integrating animal welfare, human wellbeing, and environmental sustainability into a single framework. Despite growing global recognition of One Welfare as a governance tool to address zoonotic risks, societal vulnerabilities, and ethical challenges, its practical implementation remains limited in most regions. Uruguay provides a relevant case to explore how systemic gaps in animal welfare regulation can undermine public health resilience and zoonotic disease control. Methods: We analyzed Uruguay's position in international animal welfare indexes, reviewed national animal welfare legislation and educational strategies, and conducted a systematic assessment of One Welfare-related conditions. Additionally, we identified structural risks and governance deficits linked to inadequate animal welfare practices, including zoonotic risks, through a targeted literature review and policy analysis. Results: Despite global advances in multi-species health governance, Uruguay shows legislative fragility and fragmented institutional frameworks. Key failures include outdated laws, inadequate animal-ethical perception, uncontrolled companion animal populations, deficient sterilization practices despite legal mandates, over-whelmed shelters, rising animal–vehicle collisions, culturally entrenched but underregulated hunting, illegal wildlife trade, limited veterinary oversight, and painful routine farm practices with minimal anesthesia. Gaps in surveillance and biosecurity amplify underreported zoonotic threats, reflecting a structural disconnect between One Welfare principles and policy implementation. Conclusion: To move from aspirational discourse to actionable strategies, One Welfare must be embedded as a governance instrument that enables multi-species stewardship and integrated health systems. Uruguay exem- plifies the pressing need for comprehensive, intersectoral solutions to mitigate zoonotic risks, enhance public health, and align national policies with global sustainability agendas.