The intricate and paradoxical relationship between branched-chain amino acids (BCAAs) and lipid metabolism has been focused on the field of nutrition. However, the molecular mechanism mediated by BCAAs in the lipid metabolism of fish is poorly understood. To address this knowledge gap, we characterized the transcriptome and metabolome in the liver of largemouth bass (Micropterus salmoides), an extensively cultivated fish with high commercial value. Dietary BCAA supplementation significantly enhanced growth performance, combined with the elevation of essential amino acid levels and the improvement of liver health. Moreover, enzymatic detection and RT‒qPCR results showed that BCAAs decreased lipid deposition in the liver. Integrated transcriptomics and metabolomics analysis revealed that the inhibition of lipid synthesis and enhancement of fatty acid degradation may explain the mechanism by which BCAAs relieved lipid accumulation in the liver. The metabolic enzymes acaca , acaa2 , cpt2 , acat , and aldh9a1, which were regulated by all three BCAAs, are key targets linking BCAA metabolism and lipid metabolism. Considering that farmed fish suffer from abnormal lipid accumulation in the liver, appropriate BCAA supplementation is an effective nutritional strategy to improve lipid metabolism disorders in aquaculture.