Immunization is one of the greatest public health achievements of all times, preventing millions of deaths and making major improvements in child survival in Africa. Beyond protecting against infectious diseases, vaccines foster educational attainment, productivity, and poverty reduction, while mitigating antimicrobial resistance and economic shocks. However, each year more than 9.5 million children in the World Health Organization African Region remain under-vaccinated, resulting in recurrent outbreaks of vaccine-preventable diseases. In 2024 alone, 59 outbreaks were reported across the region, including measles, variant polioviruses, meningitis, cholera, and yellow fever. To meet growing demands amid constrained resources, we propose three strategic shifts to reimagine immunization as a catalyst for resilient health systems and equitable development in Africa: (1) transitioning from vertical delivery models to integrated approaches embedded in primary health care; (2) expanding success metrics beyond coverage to include equity, resilience, and process indicators, supported by implementation science and digital innovations; and (3) reframing immunization as a whole-of-society development priority anchored in political leadership, sustainable financing, and regional vaccine manufacturing. By embracing these shifts, Africa can transform immunization into a driver of health system strengthening, equity, and sustainable development.