Childhood obesity in US Latinx and Latin American populations is a persistent, complex public health issue and, as such, requires solutions grounded on systems science theory and methods. In this paper, we introduce an action‐oriented framework to design, implement, evaluate, and sustain whole‐of‐community systems changes for childhood obesity prevention in US Latinx and Latin American populations. Our framework covers six action steps: (1) foster multisectoral team; (2) map the system, its context, and drivers; (3) envision system‐wide changes; (4) effect system‐wide changes; (5) monitor, learn, and adapt; and (6) scale and sustain. We also propose 10 principles that put human and environmental rights and systems thinking at the center of these systems‐based solutions. For each action step, we provide a list of concrete activities, methods, approaches, and examples that can be used to guide and inform the work needed to achieve the expected outputs. Finally, we discuss how a wider adoption of systems science for childhood obesity prevention among US Latinx and Latin American populations can be encouraged and sustained.