Calcium-dependent protein kinases (CDPKs) are multi-functional proteins that combine calcium-binding and signaling capabilities within a single gene product. Current studies have shown that the CDPKs regulate numerous growth and developmental processes and biotic and abiotic stress responses. Nonetheless, knowledge concerning the specific expression patterns and evolutionary history of the CDPK family in cucumber (Cucumis sativus L.) remains very limited. We, therefore, investigated the phylogenetic relationships and expression profiles of the 19 CDPK genes identified in the cucumber genome sequence, resolving them into four subfamilies based on a phylogenetic tree and gene structures. Tissue-specific expression profiles suggest that cucumber CDPK genes are involved in cucumber tissue development. An expression analysis based on qRT-PCR indicated that cucumber CDPK genes are extensively involved in abscisic acid, salt, cold, drought, heat, and waterlogging responses, possibly by different mechanisms. The fates of two paralogs after divergence were also investigated, suggesting subfunctionalization and neofunctionalization during evolution. These observations lay an important foundation for functional and evolutionary analyses of the CDPK gene family in cucurbitaceae species.