Cattle pastoralism plays a central role in human livelihood in Africa. However, the genetic history of its success remains unknown. Here, through whole-genome sequence analysis of 172 indigenous African cattle from 16 breeds representative of the main cattle groups, we identify a major taurine × indicine cattle admixture event dated to circa 750–1,050 yr ago, which has shaped the genome of today’s cattle in the Horn of Africa. We identify 16 loci linked to African environmental adaptations across crossbred animals showing an excess of taurine or indicine ancestry. These include immune-, heat-tolerance- and reproduction-related genes. Moreover, we identify one highly divergent locus in African taurine cattle, which is putatively linked to trypanotolerance and present in crossbred cattle living in trypanosomosis-infested areas. Our findings indicate that a combination of past taurine and recent indicine admixture-derived genetic resources is at the root of the present success of African pastoralism.