Large carnivores are frequently released for conservation purposes, but early efforts struggled with inadequate monitoring and reporting, resulting in poor understanding of success. Although managers have improved release practice and monitoring, the use of orphaned, captive-raised large carnivores for release remains controversial because of the potential influence of captivity and the possible lack of natural behaviours in such individuals. Yet, rehabilitating orphaned individuals for release could help mitigate pressures on vulnerable wild populations. We present a case study on the rearing, rehabilitation and release of wild-born cheetahs Acinonyx jubatus that were rescued as orphans in Namibia. Our aim was to develop a methodological framework for cheetah release planning and post-release management based on the outcome of release trials conducted during 2004–2018. Between 2001 and 2012, we rescued 86 orphaned cheetahs from the wild. Of these, 36 (42%) were selected as release candidates. We found high success rates (75–96%) of selected individuals in achieving independence post-release. Additionally, annual survival estimates for rehabilitated individuals that reached independence were comparable to those of wild counterparts described by other studies, and some rehabilitated individuals reproduced with wild conspecifics. Our findings demonstrate the ability of wild-born, captive-raised cheetahs to transition back into the wild with strategic pre- and post-release management directed towards optimizing survival. This includes selecting appropriate release candidates, forming artificial coalitions, balancing habituation levels during captivity, choosing appropriate release sites, and providing strategic support during post-release monitoring. We encourage scientists and managers to implement and refine our protocol for rehabilitation throughout the cheetah’s current and historic range.