ABSTRACTThe largemouth bass virus (LMBV) significantly impacts Chinese largemouth bass aquaculture. The molecular mechanisms regulating LMBV virulence and the gene responses stimulated in the host during infection remain unclear. This study investigates the transcriptional dynamics and signalling pathways activated during the immune response to LMBV by analysing the transcriptome of head kidney tissues at 1, 4, 7, and 28 days post‐infection (dpi) using RNA sequencing. Histopathological and viral load analyses indicated early tissue disruption, followed by extensive recovery by 28 dpi. Analysis of differentially expressed genes (DEGs) and weighted gene co‐expression network analysis (WGCNA), combined with Venn analysis of samples at 1, 4, and 7 dpi, identified significant and common genes. Early infection triggered robust innate immunity through activation of the RIG‐I like receptor and cGAS‐STING signalling pathways, which activated type I interferons (IFNs) and interferon‐stimulated genes (ISGs). Later stages indicated activation of adaptive immune responses. Validation of randomly selected genes via RT‐qPCR confirmed the RNA‐seq results, showing consistent expression patterns. This comprehensive study offers new insights into the sustained innate and adaptive immune responses to LMBV.