The goal of this theory of change is to provide funders, implementing partners, and designers a tool to increase the understanding and application of human-centered design (HCD) as an approach that enhances global health programming. The theory of change also aims to communicate the potential for HCD to introduce new and disruptive mindsets, practices, and techniques to global health programming and to clarify HCD’s potential value from the funding application process through to implementation. We seek to answer the key question: how do design and traditional global health practices and mindsets integrate to drive more people-centered, innovative solutions to health challenges and achieve common health sector and global health ecosystem goals?