BACKGROUND: Global health and development (GHD) systems that centralize power in the Global North were conceived during colonialism. As a result, they often replicate unequal power structures, maintaining dogged inequities. Growing and historic calls to decolonize GHD advocate for the transfer of power to actors in the Global South. This article identifies examples of colonial legacies in todays GHD projects and offers actionable strategies to decolonize. METHODS: From August 2021 to March 2022, 20 key informants across 15 organizations participated in interviews about their experiences and perspectives relating to the decolonization of GHD. We used deductive thematic coding to identify examples of challenges and strategies to address them across 3 project life cycle phases: conceptualization and contracting, program planning and implementation, and program evaluation and dissemination. RESULTS: Participants described how power is maintained in the Global North, sharing countless examples across the project life cycle, including agenda-setting with minimal local participation or partnership, onerous requirements that limit grantee eligibility, Global North ownership of data collected by and in the Global South, and dissemination in languages and formats that are not easily accessible to Global South audiences. Proposed strategies to decolonize GHD projects include having built-in participatory processes and accountability mechanisms; aligning solicitations with existing local strategies; adapting the process for awarding, contracting, and evaluating investments to increase the representation and competitiveness of Global South entities; creating trusting, respectful relationships with Global South partners; and systematically applying power analyses to each step of the project life cycle. CONCLUSIONS: GHD practitioners suggested project life cycle-based strategies for shifting power and redistributing resources, which we argue will ultimately enhance the value, impact, and sustainability of GHD programming.