Enset (Enseteventricosum (Welw.) Cheesman) is a multipurpose, drought-tolerant and a key food security crop, which is the staple food for peoples in the South and Southwestern parts of Ethiopia. Despite its importance, enset is an orphan crop as regards genetic research and breeding. In this study, we characterized genetic diversity, population structure and selection signatures in 226 cultivated and 10 wild enset accessions collected from diverse enset growing regions of Ethiopia using 3505 high-quality SNP markers obtained from ddRAD-sequences. The population structure and cluster analyses clearly distinguished between cultivated and wild enset. AMOVA revealed much higher levels of genetic variation within populations and regions (91.2 and 92.4%, respectively) than between populations and regions (8.8 and 7.6%, respectively). This shows that the region of origin and environmental heterogeneity have little influence on the genetic variation. However, the genetic differentiation between regions was moderate to large (FST = 0.06–0.17). The genetic structure of enset was mainly shaped by eco-geographic factors, mode of propagation and cultivation status. Six genes potentially involved in sexual reproduction and flowering signalling, which are key processes underlying domestication and adaptation, were under positive selection demonstrating that sexual reproduction plays an important role in shaping enset diversity. A lot of unexplored diversity is available for improving enset in Ethiopia, with patterns of diversity consistent with divergent selection on adaptive traits. This diversity also shows potential for introducing enset as a more food secure crop for the food insecure regions in the dry north of Ethiopia.