The political determinants of health create the structural conditions and the social drivers—including poor environmental conditions, inadequate transportation, unsafe neighborhoods, poor and unstable housing, and lack of healthy food options—that affect all dynamics involved in health. Globally, recurring examples of the role that these political determinants—through government action or inaction, and policy—are playing in health outcomes and life expectancy, particularly in under-resourced communities, can be observed currently as well as historically. Most notably, the political determinants of health are more than merely separate and distinct from social determinants of health: they serve as the instigators of the social determinants of health with which many people are already well acquainted. They involve the systematic process of structuring relationships, distributing resources, and administering power, operating simultaneously in ways that mutually reinforce or influence one another to shape opportunities that either advance health equity or exacerbate health inequities. Focusing on the political determinants of health homes in on the fundamental causes that give rise to, sustain, and exacerbate the social determinants of health that create and worsen the persistent and devastating health inequities that are observed, experienced, researched, and reported. By employing both a theoretical and practical lens to the amelioration of health inequities that continue to pervade communities across the globe, the article contextualizes many of the historic harms that have occurred throughout history, providing a unique perspective on the current state of affairs, and offering a tangible path forward toward a more equitable future. Furthermore, consideration of this new framework at all levels of government as it relates to improving health outcomes for any nation is imperative in order to eliminate existential threats for any and all populations.