The study investigated the impact of sulfate-type saline-alkali water on the growth, feed utilization, histomorphology, and liver inflammation in largemouth bass. Largemouth bass (16.5 ± 0.33 g) were divided into four groups: freshwater (CON), salinity 6‰ with 7 mmol/L alkalinity (S6A7), salinity 6‰ with 10 mmol/L alkalinity (S6A10), and salinity 9‰ with 7 mmol/L alkalinity (S9A7). Each group comprises three tanks, each containing ten fish. The experiment continued for 30 d. The results showed that sulfate-type saline-alkali water significantly reduced specific growth rate (SGR), feed intake (FI), and condition factor (CF) while increased feed conversion ratio (FCR) (P < 0.05). Compared with S6A7 group, SGR and FI were significantly lower in S6A10 and S9A7 groups, and FCR was significantly higher in S6A10 group (P < 0.05). In S6A7, S6A10, and S9A7 groups, swollen gill filaments, damaged intestinal villi, increased renal plasma cells, and signs of renal degeneration, alongside elevated serum ALT levels were observed. Hepatic pro-inflammatory gene (tnf-α, il-1β, il-6, il-8) expression was stable in the S6A7 group (P > 0.05) but significantly increased in S6A10 and S9A7 groups (P < 0.05). The anti-inflammatory genes (tgfβ-1a) were down-regulated in S6A10 and S9A7 groups (P < 0.05). Sulfate-type saline-alkali water also led to marked decline in ghr-β expression and increase in igf-1 expression (P < 0.05). In summary, sulfate-type saline-alkali water inflicts gill, intestine, and kidney damage in largemouth bass, stimulates hepatic inflammation, disrupts the GH-IGF axis, and consequently hampers the growth performance. Our findings offer a potential solution to counteract growth inhibition in fish reared in saline-alkali water, aiming to assist aquaculturists in improving productivity under challenging conditions.