Highly pathogenic avian influenza (HPAI) has evolved from episodic outbreaks into a globally entrenched, multi-host panzootic, with recurrent spillover into mammals. The expanding host range and increasing wildlife–livestock interfaces challenge traditional control strategies, increase opportunities for viral adaptation, and thereby elevate zoonotic risk. We therefore propose that HPAI should be reframed as a long-term systemic risk requiring resilience-based governance, and strengthened One Health control and preparedness.