Late wilt disease (LWD) caused by the fungus Magnaporthiopsis maydis poses a major threat to maize production. Developing high-yielding and resistant hybrids is vital to cope with this destructive disease. The present study aimed at assessing general (GCA) and specific (SCA) combining abilities for agronomic traits and resistance to LWD, identifying high-yielding hybrids with high resistance to LWD, determining the parental genetic distance (GD) using SSR markers and investigating its relationship with hybrid performance and SCA effects. Ten diverse yellow maize inbred lines assembled from different origins and three high-yielding testers were crossed using line × tester mating design. The obtained 30 test-crosses plus the check hybrid TWC-368 were evaluated in two field trials. Earliness and agronomic traits were evaluated in two different locations. While resistance to LWD was tested under two nitrogen levels (low and high levels) in a disease nursery that was artificially infected by the pathogen Magnaporthiopsis maydis. Highly significant differences were detected among the evaluated lines, testers, and their corresponding hybrids for most measured traits. The non-additive gene action had more important role than the additive one in controlling the inheritance of earliness, grain yield, and resistance to LWD. The inbred lines L4 and L5 were identified as an excellent source of favorable alleles for high yielding and resistance to LWD. Four hybrids L5 × T1, L9 × T1, L4 × T2, and L5 × T2, exhibited earliness, high grain yield, and high resistance to LWD. Parental GD ranged from 0.60 to 0.97, with an average of 0.81. The dendrogram grouped the parental genotypes into three main clusters, which could help in reducing number of generated crosses that will be evaluated in field trials. SCA displayed significant association with the hybrid performance for grain yield and resistance to LWD, which suggests SCA is a good predictor for grain yield and resistance to LWD