Nature of gene action and genetic parameters for disease resistance are important attributes in developing resistant cultivars. This provides the sustainable, economically justifiable and environmentally friendly means of controlling plant diseases. In this study, 6 x 6 full diallel cross involving genetically divergent maize inbred lines was performed with the aim of developing resistant cultivars against Maize Lethal Necrosis (MLN) disease under MLN disease hot spot areas in Mlangarini, Ngaramtoni and Kiru six in the Northern Zone of Tanzania during 2015 cropping season. The experimental materials consisted of thirty single cross hybrids, six parents and two local checks. The experiment was laid down in a randomized complete block design (RCBD) with three replications per location. The general combing ability (GCA) and specific combining ability (SCA) effects were significantly different for MLND response among genotypes across all locations. The combined analysis revealed that GCA was highly significant at P≤0.001 than SCA in all locations with mean squares of (5.551***), (1.61***) and (4.527***) for Mlangarini, Kiru six and Ngaramtoni respectively. The GCA: SCA ratios were 1.894, 1.726 and 1.403 for Mlangarini, Kiru six and Ngaramtoni respectively. The implication of GCA/SCA ratio of more than a unity proves that GCA is significant in all locations where this study was conducted. The results also revealed the presence of both additive and non-additive genetic effects, with the former more pronounced than the later. This implies that developing composite variety will be the better option in combating the disease. However the best cross was observed between CML 144 X CML444 with mean square -0.10, -0.45* and -0.18* for Mlangarini, Kiru six and Ngaramtoni respectively.