This comprehensive message guide supports multisectoral communication and behavior change efforts for the prevention and control of five priority zoonotic diseases in Ethiopia: anthrax, brucellosis, rabies, Rift Valley fever, and highly pathogenic avian influenza. Developed through a participatory and government-led process, the guide was facilitated by Ethiopia’s National One Health Steering Committee with technical contributions from Breakthrough ACTION Ethiopia. It offers harmonized, audience-specific messages designed to reduce risky behaviors, promote early treatment-seeking, and encourage protective actions among livestock owners, community members, and frontline health workers. Grounded in the One Health approach, the guide ensures consistent messaging across sectors and communication channels during both routine and emergency response periods.