Lettuce is a highly nutritional crop that is sensitive to multiple stresses, including salt stress. The decreasing availability of salt-free water is posing a major challenge to growing nutritious lettuce in hydroponic systems. Despite evidence that salt stress affects yield and nutrition, its impacts on economically important growth stages are overlooked. This study addressed the knowledge gaps regarding the salt stress impact on romaine lettuce. Four independent experiments were conducted in controlled environment conditions using 2-38 lettuce genotypes, to assess the effects of salt stress at rosette or head formation. An increase in sodium chloride (NaCl) levels (0 to 150 mM) linearly decreased lettuce biomass. A positive association was observed between NaCl and sodium to potassium ion ratio. Lettuce was found to be sensitive to salt above 40 mM NaCl. The phenotyping of 38 lettuce genotypes revealed significant variability in salt stress tolerance. Genotype, Green forest exhibited a higher decline in fresh and dry biomass compared to Burgundy delight, indicating its higher sensitivity to salt stress. Sodium accumulation was significantly higher in both genotypes under salt stress, while potassium decreased in Green forest but remained relatively stable in Burgundy Delight. Hydro-primed lettuce had higher photosynthetic efficiency and oxidative stress tolerance than the control. Hydro-priming seed treatment could be used as a cost-effective priming technique to boost economic efficiency under stress. In addition, the low sodium: potassium ratio and high biomass can be used as indicators for selecting salt-tolerant genotypes.