ABSTRACT Powdery mildew (PM) is a serious fungal disease in plant cultivation, which is detrimental to the yield and quality of oriental melons. Lipoxygenases (LOXs) are widely involved in pathogen stress response. Our previous studies have indicated that red light (RL) can induce defense to PM in oriental melon seedlings. However, it remains unclear whether LOXs are involved in this process. In this study, we found that LOX activity is essential for RL‐induced PM resistance, with CmLOX10 is identified as a key member. We conducted a yeast one‐hybrid (Y1H) screening of oriental melon cDNA libraries using the CmLOX10 promoter, which led to the identification of CmWRKY41 and CmABL5. Both of these proteins can regulate the expression of CmLOX10 , thereby participating in the RL‐induced PM resistance process. Furthermore, phytochrome B (phyB) interacts with CmABL5 at the protein level, enhancing its transcriptional activation of CmLOX10 . Silencing CmphyB undermines the induction of RL resistance to PM. Our study elucidates the activation mechanism of CmLOX10 involved in PM resistance following RL induction, thereby enriching the network of interaction between light and pathogenic fungi.