Background: The COVID-19 pandemic has underscored the importance of understanding the transmission dynamics of the virus between humans and animals. The One Health model, which recognizes the interconnectedness of human, animal, and environmental health, is crucial for understanding and addressing zoonotic diseases. This scoping review aims to explore the literature on animal-to-human transmission of COVID-19 in Southern Africa, with a focus on identifying neglected facets in transmission dynamics informed by the One Health model. Methods: A scoping review of empirical studies and surveillance reports from December 2019 to December 2024 was conducted. Eligible literature addressing SARS-CoV-2 infection in domestic animals within Southern Africa was systematically identified, charted using a structured extraction template, and synthesized narratively through thematic analysis. Results: The findings demonstrate that dogs and cats are the most consistently vulnerable domestic species in Southern Africa, with infections varying from asymptomatic to mild symptomatic cases. Limited and sporadic evidence suggests potential exposure in livestock species, including cattle, though data remain scarce. Genomic surveillance in South Africa has further revealed the emergence of Omicron lineages, underscoring the risk of variant evolution at the human–animal interface. Comparatively, Europe and North America have reported severe outbreaks in farmed mink, prompting large-scale culling, while Asia has emphasized wildlife market regulations and biosecurity measures. Conclusion: Southern Africa demonstrates strengths in genomic monitoring and case-based detection but faces the challenges of limited infrastructure, small sample sizes, and geographic gaps. Strengthening coordinated One Health surveillance, expanding animal testing, and addressing geographic and infrastructural gaps are essential to reduce spillover risks and improve preparedness for future zoonotic threats.