Low levels of physical activity can have adverse effects on youth development due to increased risks for many chronic illnesses and medical conditions. Improving physical literacy (PL), or the ability to move with competence and confidence in a wide variety of physical activities within multiple environments, can shape a path of healthy development for youth. According to cumulative disadvantage theory, inequalities accumulate and manifest over the course of one's life through demographic and developmental processes. We believe that systematically enhancing PL among youth with chronic disease will dramatically reduce existing health disparities caused by low levels of physical activity. We propose four recommendations for improving PL among youth living with chronic disease: (1) explore and create culturally appropriate instruments that can reliably measure PL among disadvantaged youth with chronic disease; (2) mandate updated PL curricula in underperforming US schools; (3) establish community-based out-of-school-time (OST) PL initiatives for U.S. youth with chronic disease in under resourced communities; and (4) invest in sustainable OST PL programs that target this vulnerable subpopulation. We believe taking these next steps will reduce health-related inequalities. Thus, Health Education specialists should advocate for health promotion initiatives that foster optimal PL among disadvantaged youth living with chronic disease.