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CBP60b (CALMODULIN-BINDING PROTEIN 60b) is a member of the CBP60 transcription factor family. In Arabidopsis, <i>At</i>CBP60b not only regulates growth and development but also activates the transcriptions in immune responses. So far, CBP60b has only been studied extensively in the model plant Arabidopsis and rarely in crops. In this study, <i>Bean pod mottle virus</i> (BPMV)-mediated gene silencing (BPMV-VIGS) was used to silence <i>GmCBP60b.1/2</i> in soybean plants. The silencing of <i>GmCBP60b.1/2</i> resulted in typical autoimmunity, such as dwarfism and enhanced resistance to both <i>Soybean mosaic virus</i> (SMV) and <i>Pseudomonas syringae</i> pv. glycinea (<i>Psg</i>). To further understand the roles of <i>Gm</i>CBP60b in immunity and circumvent the recalcitrance of soybean transformation, we generated transgenic tobacco lines that overexpress <i>GmCBP60b.1</i>. The overexpression of <i>GmCBP60b.1</i> also resulted in autoimmunity, including spontaneous cell death on the leaves, highly induced expression of PATHOGENESIS-RELATED (<i>PR</i>) genes, significantly elevated accumulation of defense hormone salicylic acid (SA), and significantly enhanced resistance to <i>Pst</i> DC3000 (<i>Pseudomonas syrangae</i> pv. tomato DC3000). The transient coexpression of a luciferase reporter gene driven by the promoter of soybean SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (<i>GmSARD1</i>) (<i>ProGmSARD1::LUC</i>), together with <i>GmCBP60b.1</i> driven by the 35S promoter, led to the activation of the LUC reporter gene, suggesting that <i>Gm</i>CBP60b.1 could bind to the core (A/T)AATT motifs within the promoter region of <i>GmSARD1</i> and, thus, activate the expression of the LUC reporter. Taken together, our results indicate that <i>Gm</i>CBP60b.1/2 play both positive and negative regulatory roles in immune responses. These results also suggest that the function of CBP60b is conserved across plant species.