SUMMARY Salt stress induces cytoplasmic calcium (Ca 2+ ) ion spikes and activates Ca 2+ / calmodulin (CaM) signaling in plant cells. Calmodulin‐binding transcription activators (CAMTAs) are pivotal components of Ca 2+ /CaM‐mediated abiotic stress responses. Nevertheless, how Ca 2+ /CaM specifically interacts with the OsCAMTAs family members to modulate salinity tolerance is largely undetermined in rice. Through integrated molecular genetics, biochemical, and physiological analyses, we demonstrated that OsCaM1/2/3 interacted specifically with OsCAMTA1/2/4/6 in a Ca 2+ ‐dependent manner. Transgenics showed OsCaM1‐1 and OsCAMTA1 enhanced salinity tolerance in rice. RNA‐sequence (RNA‐seq) profiling of oscamta1 lines suggested that OsCAMTA1 positively regulates salinity tolerance by orchestrating downstream targets involved in Ca 2+ binding, hormonal responses, transcriptional regulation, and salt stress pathways. The dual‐luciferase (LUC) assays identified that OsCaM1 activates the transcriptional activity of OsCAMTA1 to the targets OsDREB1B and OsCML16 , respectively, both of which positively regulate the salinity tolerance in rice seedlings. Transcriptomic screening revealed that OsCAMTA1 and OsDREB1B co‐regulated the genes OsZFP179 , OsMST4 , and Oshox22 , while OsCAMTA1 and OsCML16 co‐regulated the genes OsP5CS , OsABI5‐1 , and OsHAK24 under salt stress. Our study reveals a novel OsCaM1‐OsCAMTA1 module to regulate the OsDREB1B/OsCML16 transcriptional cascade under salt stress, providing candidate genes for breeding salt‐adapted rice varieties in the future.