Calmodulin (CaM) and calmodulin-like (CML) proteins, a group of Ca2+ sensors, play an important role in a large number of different biological processes, including plant growth and development, as well as the biotic and abiotic stress responses. However, CaM/CML genes have not been identified in sacred lotus (Nelumbo nucifera), an important horticultural plant, and the expressional patterns of these genes are yet to be elucidated. In this study, thirty-four CaM/CML genes from Nelumbo nucifera were identified. Phylogenetic analysis showed that they could be divided into nine groups. Gene structure and conserved motif analyses demonstrated the conservation and divergence of CaMs/CMLs in Nelumbo nucifera. Cis-acting elements analysis indicated that they might be related to plant growth and development, abiotic stress, and plant hormones. In addition, expression analysis showed that NNU-CaMs/CMLs were differentially expressed in various tissues and responded to calcium treatments in roots. Moreover, weighted gene co-expression network analysis of public transcriptome data of lotus wild variety "China Antique" with different tissues presented the expression connectivity of NNU-CaMs/CMLs, which were divided into 11 modules. Gene ontology analysis of the genes in each module demonstrated that NNU-CaMs/CMLs may be involved in extensive biological processes, such as synthesis and processing of DNA and RNA, and protein post-translational modification, and each module specifically correlated with the phenotypes including the development of leaves' petiole and lotus seed, implying the wide regulation of NNU-CaMs/CMLs in lotus. Taken together, our results will enhance the understanding and lay a foundation for further study of the functions of the NNU-CaMs/CMLs.