This study assessed the variations in grain yield (GY) and protein content (PC) within two commercial durum wheat cultivars (Svevo and Maestrale) and evaluated their responses to intra-cultivar selection for both traits. We investigated whether the variations are exploitable and could result in concurrent GY and PC upgrading. The experiments were conducted in the IPBGR, Thessaloniki, Greece (2018–2020). The first year included two identical honeycomb design trials under ultra-low plant density (ULD) where the divergent selection was applied based on single plant yield and protein content. In the second year, progeny evaluation under typical crop density (TCD) for GY and PC occurred in a randomized complete block (RCB) and with three replications for each cultivar selected line. This revealed considerable variation within already improved commercial cultivars. Single-plant selection for GY and PC simultaneously resulted in: (a) one high-yielding line that significantly outperformed the original cultivar Svevo while maintaining high PC, and (b) two high-grain PC lines that outperformed the original cultivar Maestrale significantly while maintaining high GY. ULD allowed efficient selection for GY and PC simultaneously within narrow gene pools by maximizing phenotypic expression and differentiation among individual plants.