The objective is to discern how Charles Darwin’s Origin of species (1859) and the theory of natural selection and evolutionary biology – ‘a grain in the balance will determine which individual shall live and which shall die’– are core to achieving environmentally and climate-smart, economically viable, sustainable animal agriculture in a changing climate. Darwin’s ‘survival of the fittest’ theory implies inherent comparative advantage of survivors over the succumbed in any given environment. An animal’s phenotype (P) results from interaction of its genotype (G) and the environment (E), expressed as P = G x E. Human migration has transferred livestock breeds from places of origin to distant continents and agro-ecological zones, far from where they have inherent comparative production advantage. For example, crossbreeds of Bos taurus and Bos indicus have higher average performance than median of either parent population. However, the heterotic effect of hybrids is associated with loss of environmental adaptation compared with parent populations. Indigenous breeds, their phenotypes and ecotypes thrive best in distinct environments, ceteris paribus. An environment is the sum total of conditions that influence animal productivity in the habitat. These include nutrition, genetics, disease, exposure to parasites, management practices, climate, rainfall, humidity, heat and cold stressors, and advisory services. Hybrids lose some adaptive capacity compared with parents, and require habitat modifications if they are to express their fullest genetic potential. In the light of this and of global warming challenges to livestock production, it is scientifically and technically prudent to exploit the inherent comparative production advantages of indigenous genotypes, phenotype and ecotypes, when mitigating climate change, more so in low-input animal agriculture systems of sub-Saharan Africa and at similar locations. Climate change poses multidisciplinary challenges that require integrated collaborative cross-discipline research, extension and training to provide holistic solutions.