Increasing water temperatures and salinity intrusion due to climate change are serious challenges for freshwater aquaculture. In this study, we assessed the combined effects of salinization at 0, 6, and 9‰ and water temperatures of 28, 31, and 34 °C on the survival and growth rates, and feed utilization, of freshwater snakehead Channa striata. We also assessed feed digestibility in snakeheads to explore their physiological mechanisms. The lowest survival rate (66.7%) was found at 34 °C-9‰. The highest daily weight gain of 0.72 g/day was found at 34 °C-0‰, while the second highest (0.62 g/day) was at 31 °C-0‰. Chymotrypsin activity increased at higher temperatures; the activities of α-amylase and pepsin were lowest at 34 °C-9‰. The highest apparent digestibility coefficients (ADCs) for dry matter (80.3%), protein (95.3%), and lipid (97.9%) were observed at 31 °C-0‰ (p < 0.05). Elevated temperature (34 °C) combined with high salinity (9‰) was lethal for one-third of the fish. The lowest ADC and α-amylase activities led to the highest feed-conversion ratio. Snakehead growth rates were highest in the 31 °C-0‰ and 34 °C-0‰ treatments. The combined highest salinity and highest temperature treatment (34 °C-9‰) decreased snakehead growth, feed utilization efficiency, feed digestibility, and enzyme activities (except for chymotrypsin).