Background/Objectives: The USAID STOP Spillover project in Cambodia aimed to reduce the risk of zoonotic virus spillover from bats to humans in bat guano farming communities. Methods: Using participatory tools, such as Outcome Mapping and Trials of Improved Practices, a team of local experts and community members collaboratively designed, tested, and refined biosafety and hygiene practices that are acceptable and sustainable to mitigate the risk of bat-borne disease spillover. We tracked progress and rolled out interventions to promote the adoption of safe behaviors that strengthen the understanding of zoonotic disease and reinforce the adoption of safety practices among bat guano producers and their neighbors. The intervention’s effectiveness was evaluated after three-month trials. Results: An improvement in knowledge, attitudes, and risk reduction practices was observed among participants. The primary motivators for adopting these measures were fear of disease, families’ well-being, cost savings, and experience of the COVID-19 pandemic. Conclusions: The community-driven approach fostered a sense of ownership, enabling participants to find the best solutions for their circumstance for long-term sustainability of the intervention. The findings recommended continued community engagement, improved access to biosafety and hygiene resources, and reinforced routine zoonotic disease surveillance. This model can be applied to mitigate emerging infectious disease spillover risks in similar contexts.