The Nile tilapia Oreochromis niloticus is native to Africa and middle East, and is an important source of nutrition for many in sub-Saharan Africa. Understanding the genetic diversity within and differentiation among wild populations can help identify O. niloticus populations that are imperiled and require directed management, especially because of increasing threats to the species' long-term persistence in the wild, including habitat destruction, overfishing, climate change, and hybridization with farmed populations. Knowledge of the genetic variation among wild populations also can contribute to foundation and selection of genetically diverse populations for aquaculture. I assessed the genetic variation among tilapia populations using fin-clips collected between December 2014 and July 2017 from 14 farmed sources, mostly originating from cage farms on the Volta Lake, and 13 wild sources from nine river basins in Ghana. I also conducted a laboratory growth experiment in Ghana with two wild populations to evaluate the tolerance of different genotypes to high temperatures, to inform their development for aquaculture in West Africa. I found that pure O. niloticus populations persist in the wild but some have been extensively introgressed with the closely related species, O. aureus, which has not previously been documented in Ghana. Additionally, some wild populations appear to have recently declined significantly in numbers, likely due to overfishing and habitat modification, the latter primarily as a result of illegal alluvial mining ongoing in Ghana. Analysis of the farmed populations revealed that at least two farms were growing the unapproved genetically improved farmed tilapia (GIFT) and related strains, and that escaped individuals are admixed into some wild populations. The results of my laboratory experiment showed that O. niloticus populations occurring in northern Ghana already may be adapted to warmer temperatures and could be developed and used purposefully in aquaculture, taking advantage of their adaptation. To protect remnant pure O. niloticus populations in the wild, timely conservation decisions should be made and implemented. Protecting wild O. niloticus populations also would ensure that pure germplasms are available to develop aquaculture stocks from native populations.