The calmodulin-binding protein 60 (CBP60) family comprises essential Ca²⁺-responsive transcription factors that orchestrate salicylic acid (SA)-mediated immunity and broader stress responses. Despite being extensively characterized in model species, the CBP60 family remains poorly understood in watermelon (Citrullus lanatus), a globally significant cucurbit crop highly susceptible to aphid infestation and fusarium wilt. In this study, we performed a comprehensive genome-wide identification and characterization of the CBP60 gene family in watermelon, identifying 16 putative ClaCBP60 members, all of which harbor the conserved calmodulin-binding domain. These genes are non-randomly distributed across chromosomes, featuring a prominent cluster of 10 members on chromosome 3. Phylogenetic analysis across seven cucurbit species categorized the CBP60 proteins into four distinct subfamilies, revealing both evolutionary conservation and lineage-specific diversification. Gene structure and conserved motif analyses revealed shared core domains with subfamily-specific variations, indicative of functional divergence. Furthermore, synteny analysis showed strong collinearity with cucumber and melon, reflecting the evolutionary stability of key CBP60 loci. Transcriptional profiling under F. oxysporum infection and aphid infestation revealed dynamic expression patterns, with ClaCBP60_01 and ClaCBP60_16 exhibiting rapid and robust induction during the early stages of both stresses. These findings indicated that ClaCBP60 genes operate in a coordinated yet diversified manner to modulate defense signaling against F. oxysporum and aphid attack. This study provides a systematic insight into CBP60 family members in watermelon, establishing a foundation for validation and molecular breeding aimed at enhancing biotic tolerance.