Soil salinization is a major environmental stress that restricts plant growth and reduces crop yields. Developing salt-tolerant crop varieties using classical, molecular genetics methods and understanding the mechanisms of salt resistance is essential for sustainable crop improvement. This study evaluated seed germination and vegetative morphology of upland cotton (Gossypium hirsutum L.) under model salt stress, comparing Uzbek classical breeding varieties of AN-Bayovut-2, Tashkent-6, Namangan-77 and the Coker-312 variety with biotechnological knock-out varieties of the Porloq series viz. Porloq-1, Porloq-2, Porloq-3 and Porloq-4. An analysis of the results of seed germination parameters: relative germination (RG), average germination time (AGT), germination index (GI) and germination energy (GE) showed that the most resistant to salinity (NaCl concentrations— 50, 100, 150 and 200 mM) was the biotechnological gene-knockout Porloq-4 variety and the least resistant was the Coker-312 variety of classical breeding. A study of morphological parameters showed that 100 mM NaCl causes a slowdown in the growth of roots and shoots, as well as biomass gain in both genotypes. However, in the Porloq-4 biotechnological variety, the negative effects of NaCl were less pronounced compared to the salt-sensitive Coker-312 variety.