Plant disease management is key to sustainable production of staple food crops. Calcium (Ca²⁺) signal and phytohormones play critical roles in regulating plant defense responses against pathogens. The Ca²⁺ signals are sensed, decoded and transduced by calmodulin and other Ca²⁺ -binding proteins, followed by interaction with and modulation of activities of target proteins such as calmodulin-binding proteins (CBPs). Members of the Arabidopsis CBP60 gene family, AtCBP60g and AtSARD1, have emerged as major regulators of immune responses. In this study, we identified a 15 member CBP60 gene family in rice (Oryza sativa) of which OsCBP60g-3, OsCBP60g-4, OsCBP60a and OsSARD-like1 genes were consistently upregulated in rice seedlings in response to infection with both fungal (Magnaporthe oryzae) and bacterial (Xanthomonas oryzae) pathogens as well as by salicylic acid (SA). OsCBP60g-4 and OsCBP60g-3 were induced maximally by SA and brassinosteroid (BR), respectively, and OsCBP60g-4 was expressed at 3-fold higher levels in the M. oryzae resistant rice genotype (IC-346004) as compared to the susceptible rice genotype (Rajendra Kasturi). The considerable expansion of the immunity clade and the up-regulation of several OsCBP60 genes in response to pathogens and defense hormones supports the importance of further investigating OsCBP60 genes as targets for increasing disease resistance in rice.