Climate change is a major influencing factor in beef production. The greenhouse gases produced from livestock production systems contribute to the overall greenhouse gas emissions. The aim of this study was to identify selection signatures within and between Nguni and Bonsmara cattle in relation to production and adaptation. For this purpose, genomic 150 K single nucleotide polymorphism data from Nguni (n = 231) and Bonsmara (n = 252) cattle in South Africa were used. Extended haplotype homozygosity (EHH) based analysis was executed within each population using integrated haplotype score (iHS). The R package rehh was used for detecting selection signatures across the two populations with cross population EHH (XP-EHH). Total of 121 regions of selection signatures were detected (p < 0.0001) in the Bonsmara and Nguni populations. Several genes relating to DNA methylation, heat stress, feed efficiency and nitrogen metabolism were detected within and between each population. These regions also included QTLs associated with residual feed intake, residual gain, carcass weight, stature and body weight in the Bonsmara, while QTLs associated with conception rate, shear force, tenderness score, juiciness, temperament, heat tolerance, feed efficiency and age at puberty were identified in Nguni. Based on the results of the study it is recommended that the Nguni and Bonsmara be utilized in crossbreeding programs as they have beneficial traits that may allow them to perform better in the presence of climate change. Results of this study coincide with Nguni and Bonsmara breed characteristics and performance, and furthermore support informative crossbreeding programs to enhance livestock productivity in South Africa.