ABSTRACTMelon holds significant economic importance for Brazilian agribusiness. It exhibits high polymorphism and genetic variability, yet knowledge regarding its genetic diversity and response to root diseases remains limited. Therefore, this study aimed to assess the genetic diversity and response of melon plant accessions to Monosporascus cannonballus. Two trials were conducted involving 29 melon accessions and a commercial hybrid of the yellow melon plant, Natal RZ. In the first trial, the accessions and the commercial hybrid were grown in the field under a randomised complete block design with three replications. They were evaluated for fruit‐related descriptors: number of fruits per plant (NFP), average fruit weight, shape index, pulp thickness, pulp firmness (PF) and total soluble solids (TSS). Standardised Euclidean distances were calculated on the basis of the results, and the accessions were grouped using the UPGMA method. In the second trial, the melon plant accessions and commercial hybrid were cultivated in a greenhouse under a completely randomised design with 12 replications. For inoculation, wheat grains infested with M. cannonballus isolate CMM‐2429 were used. Evaluations were conducted 60 days after transplanting, assessing the incidence and severity of the disease, and biometric variables. The study revealed genetic variability among the evaluated accessions for fruit descriptors and response to M. cannonballus. Most divergent accessions were A16, A53, NZR, A28, A51 and A44, with divergence primarily observed in NFP, PF and TSS. Promising accessions for breeding programmes aimed at resistance to M. cannonballus included A01, A04, A25, A27 (moderately resistant) and A26 (highly resistant to the pathogen).