Ozark hellbender (Cryptobranchus alleganiensis bishopi, Grobman 1943) populations in Missouri and Arkansas have been federally listed as endangered since 2011. As part of the comprehensive recovery plan for the subspecies, the Saint Louis Zoo WildCare Institute's Ron and Karen Goellner Center for Hellbender Conservation, in collaboration with the Missouri Department of Conservation, Arkansas Game and Fish Commission, and the U.S. Fish and Wildlife Service, established a conservation breeding and head‐starting program to augment and create self‐sustaining wild populations. We examined how the river of origin and egg origin (i.e., Zoo‐bred or wild‐bred) influenced various growth and mortality responses of Zoo‐reared Ozark hellbenders. River of origin significantly predicted most larval and long‐term Zoo‐reared Ozark hellbender growth responses, with our results concurring with observed differences in wild populations and known genetic relationships between Ozark hellbender populations. Mortality of Zoo‐reared Ozark hellbenders was often predicted by river of origin and egg origin with Zoo‐bred hellbenders having significantly higher proportional mortality responses relative to wild‐bred hellbenders. Further exploration of this egg origin relationship revealed differences between the Zoo breeding group generations with higher proportional mortality rates for hellbenders from the less mature second‐generation breeding group relative to hellbenders from the first‐generation breeding group and wild‐bred hellbenders. Ultimately, our results provide baseline data on Zoo‐bred and wild‐bred Ozark hellbenders in the program, help identify differences in growth and mortality responses between Ozark hellbender populations, and contribute to existing evidence supporting distinct populations of Ozark hellbenders in Missouri to aid in targeted conservation strategies.