Cysteine-rich receptor-like kinases (CRKs) took crucial roles in plant cell growth and development, as well as environmental adaption. Apple (Malus domestica) had been considered a staple fruit crop and a model of woody plants. In this study, the annotation, evolution, and duplication of the CRK gene family members in apple (MdCRK) were characterized. Besides, we also investigated the expressional patterns of MdCRKs in various tissue types and response to signals from Alternaria alternate apple pathotype (AaAP), Penicillium expansum (Pe), and Valsa mali (Vm). A total of 36 MdCRKs were annotated. The phylogenetic analysis of CRKs among apple, Arabidopsis thaliana, rice (Oryza sativa), cotton (Gossypium hirsutum), banana (Musa acuminata), and tomato (Solanum lycopersicum) revealed the distinct evolutionary characteristics in plants. Based on gene duplication analysis, seven tandem gene clusters containing 24 members and ten segmental gene pairs were found from MdCRKs. A large number segmental gene pairs were identified from CRKs between apple and cotton. Abscisic acid (ABA) and methyl jasmonate (MeJA)–responsive cis-elements were discovered from the promoter region of most MdCRKs. MdCRKs showed distinct tissue and developmental expression patterns. Most members displayed distinct expression patterns among various tissue types. Six members were differentially expressed in response to signals from at least two pathogenic fungi. Our study provides valuable information for further studies on the evolution and functional investigation on disease resistance of CRKs.