Lack of freshwater is emerging as the most critical natural resource issue facing humanity. Ongoing climate change will reduce freshwater supplies, and demand for food continues to expand rapidly. Swim-up channel catfish, Ictalurus punctatus, fry transgenic for the channel catfish growth hormone (GH) gene driven by the rainbow trout Oncorhynchus mykiss metallothionein promoter (rtMT-ccGH), or by the ocean pout Zoarces americanus antifreeze protein promoter (opAFP-ccGH), channel catfish, and albino channel catfish were grown at 0, 2.5, 5, and 7.5 parts per thousand (ppt) salinity. Survival was 100% for all genetic groups at 0 and 2.5 ppt. Increasing salinity to 5 ppt decreased overall survival as survival rates of rtMT-ccGH transgenic (T), rtMT-ccGH control (C), opAFP-ccGH transgenic (T), opAFP-ccGH control (C), channel catfish, and albino channel catfish were 83, 82, 83, 77, 89 and 40%, respectively. Increasing salinity to 7.5 ppt had a strong negative impact on survival as means for rtMT-ccGH (T), rtMT-ccGH (C), opAFP-ccGH (T), opAFP-ccGH (C), channel catfish, and albino channel catfish were 67, 13, 67, 10, 18, and 7%, respectively with the albino channel catfish having the lowest survival followed by opAFP-ccGH (C) (P = .002). Raising salinity to 2.5 ppt greatly increased the growth rate of GH transgenic channel catfish (11–33%), channel catfish (56%), and albino channel catfish (124%). NaCl had a negative effect on survival and growth rate for swim-up fry at 5 ppt. Significant differences were observed at varying salinity (P < .0001) for final body weights among genetic groups. Condition factor, growth and survival were not perfectly correlated, and genotype-environment interactions occurred for the overall phenotype. Apparently, GH can play a critical positive role for channel catfish under osmotic stress, which has relevance for aquaculture management under future global climate change. Optimum performance for all genotypes was observed with slightly elevated, 2.5 ppt. Although, GH transgenic catfish were less affected than non-transgenic channel catfish at 5–7.5 ppt, their performance was sub-optimal. GH transgenic fish are beneficial for use in culture environments that have slight shifts in salinity in the future, but they are only a partial solution for future environments at 5 ppt and higher.