The Gametophytic Self-Incompatibility (GSI) system in diploid potato (Solanum tuberosumL.) poses a substantial barrier in diploid potato breeding by hindering the generation of inbred lines. One solution is gene editing to generate self-compatible diploid potatoes which will allow for the generation of elite inbred lines with fixed favorable alleles and heterotic potential. TheS-RNaseandHTgenes have been shown previously to contribute to GSI in the Solanaceae family and self-compatibleS. tuberosumlines have been generated by knocking outS-RNasegene with CRISPR-Cas9 gene editing. This study employed CRISPR-Cas9 to knockoutHT-Beither individually or in concert withS-RNasein the diploid self-incompatibleS. tuberosumclone DRH-195. Using mature seed formation from self-pollinated fruit as the defining characteristic of self-compatibility,HT-B-only knockouts produced little or no seed. In contrast, double knockout lines ofHT-BandS-RNasedisplayed levels of seed production that were up to three times higher than observed in theS-RNase-only knockout, indicating a synergistic effect betweenHT-BandS-RNasein self-compatibility in diploid potato. This contrasts with compatible cross-pollinations, whereS-RNaseandHT-Bdid not have a significant effect on seed set. Contradictory to the traditional GSI model, self-incompatible lines displayed pollen tube growth reaching the ovary, yet ovules failed to develop into seeds indicating a potential late-acting self-incompatibility in DRH-195. Germplasm generated from this study will serve as a valuable resource for diploid potato breeding.