A competitive hybrid breeding for enhanced yield is currently a hot topic in the wheat community. However, one of the major bottlenecks in hybrid production is the lack of cost-effective seed process and low heterosis. Therefore, information about the quantitative genetic parameters and the heterosis level should help to better define a breeding strategy for high yielding and disease resistant varieties. Given that yellow rust is the most devastating fungal disease across the Central and West Asia and North Africa region, hybrid breeding could be a promising approach to substantially enhance the level of yellow rust resistance in wheat. Our objectives were to (1) estimate the genetic parameters for yield, disease severity (DS) and coefficient of infection (CI), (2) compare the potential of the prediction of hybrid performance based on parental lines per se and general combining ability (GCA), and (3) investigate the potential of hybrid prediction for yellow rust resistance. Thirty-six elite spring bread wheat genotypes were selected based on their phenotypic performance for potential hybrid traits and for their response to yellow rust under field conditions for two seasons at ICARDA station Marchouch, Morocco. The parental lines were geneotyped by whole genome scanning using 15K Single Nucleotide Polymorphism (SNP) marker array. 114 F1 hybrids were developed using a partial diallel design. We observed significant phenotypic variation and moderate to high heritability for the assessed traits. The mean performance of the hybrids was superior for yield (13.09%), DS (-25.15%) and CI (-26.98%). The correlation between the line per se and the GCA effects was significant with r=0.52, r=0.63 and r=0.66 (P< 0.05) for yield, DS and CI, respectively. The sums of the GCA effects were moderately correlated with their observed hybrid performance which might be used as indicator for yield and yellow rust resistance. The accuracy of genomic predictions obtained for the three traits was between 0.56 and 0.67 which suggests the feasibility of using genomics to develop potential lines and hybrids that combine yield potential disease resistance.