Orange-fleshed sweetpotato (OFSP) is an effective, low-priced, and sustainable source of β-carotene (provitamin A). However, most OFSP varieties have low storage root dry matter content (DMC), which influences their acceptance by small-scale farmers and hence needs to be improved. The objective of the study was to determine the combining ability, type of gene action, heterosis and heritability of storage root DMC, β-carotene content, and yield-related traits of selected sweetpotato clones for further evaluation and breeding. Crosses were conducted using a 7 × 7 half-diallel mating design and a total of 28 genotypes (seven parents and 21 crosses) were evaluated at four locations in Ethiopia using a 7 × 4 alpha lattice design with two replications. The performance of the genotypes was significantly different (P < 0.01) across the four locations for storage root DMC, β-carotene content, sweetpotato virus disease (SPVD) reaction, storage root yield, and harvest index (HI). The general combining ability (GCA) and specific combining ability (SCA) mean squares were significant (P < 0.01) for all traits except the SCA effect of storage root DMC. The GCA to SCA variance ratios were 0.96, 0.94, 0.74, 0.96, and 0.97 for storage root DMC, β-carotene content, SPVD, fresh storage root yield, and HI, respectively, indicating that the inheritance of these traits was controlled mainly by additive genes. Progenies of crosses involving Ukerewe × Ejumula, Ukerewe × Pipi, Resisto × Pipi, and Ejumula × Pipi exhibited high levels of positive heterosis for storage root DMC. Similarly, progenies of crosses including Resisto × Pipi and Resisto × Ogansagan had higher positive heterosis for fresh storage root yield, reflecting the breeding value of these parents. Relatively high narrow sense heritability (h2) was obtained for β-carotene content (79.8%) and HI (48.6%). However, the h2 estimates of storage root DMC, SPVD, and fresh storage root yield were relatively low at 19.0%, 14.9%, and 20.4%, respectively. Crosses with high β-carotene content such as Ukerewe × Resisto, Resisto × Ogansagan, Eumula × Pipi, and NASPOT 1 × Temesgen exhibited high storage root DMC. These families also had medium-to-high mean fresh storage root yield. Therefore, progenies derived from these families are good candidates to develop improved OFSP varieties with high storage root DMC.