Sweetpotato is a highly heterozygous hybrid, and populations of orange-fleshed sweetpotato (OFSP) have a considerable importance for food security and health. The objectives were to estimate heterosis increments and response to selection in three OFSP hybrid populations (H1) developed in Peru for different product profiles after one reciprocal recurrent selection cycle, namely, H1 for wide adaptation and earliness (O-WAE), H1 for no sweetness after cooking (O-NSSP), and H1 for high iron (O-HIFE). The H1 populations were evaluated at two contrasting locations together with parents, foundation (parents in H0), and two widely adapted checks. Additionally, O-WAE was tested under two environmental conditions of 90-day and a normal 120-day harvest. In each H1, the yield and selected quality traits were recorded. The data were analyzed using linear mixed models. The storage root yield traits exhibited population average heterosis increments of up to 43.5%. The quality traits examined have exhibited no heterosis increments that are worth exploiting. The storage root yield genetic gain relative to the foundation was remarkable: 118.8% for H1-O-WAE for early harvest time, 81.5% for H1-O-WAE for normal harvest time, 132.4% for H1-O-NSSP, and 97.1% for H1-O-HIFE. Population hybrid breeding is a tool to achieve large genetic gains in sweetpotato yield via more efficient population improvement and allows a rapid dissemination of globally true seed that is generated from reproducible elite crosses, thus, avoiding costly and time-consuming virus cleaning of elite clones typically transferred as vegetative plantlets. The population hybrid breeding approach is probably applicable to other clonally propagated crops, where potential for true seed production exists.