Salt stress (SS) refers to excessive soluble salt concentrations in the plant root zone. SS also causes cellular water deficits, ion toxicity, and oxidative stress in plants, all of which can cause growth inhibition, molecular damage, and even plant mortality. Lettuce (Lactuca sativa L.) has a threshold electrical conductivity of 1.3–2.0 dS/m. Thus, this research focused on physiological, morphological, and biochemical attributes in multiple lettuce genotypes under SS compared to plants grown under control conditions. The experiment was arranged in a randomized complete block design with four replications. One month after planting, the salt treatment was applied at the rate of 100 millimoles (mM). The 0 mM salt in water treatment was considered the control. A significant effect of SS on different morphological and physiological traits was observed in one-month-old lettuce plants. PI 212099, Buttercrunch-1, and PI 171676 were highly salt-tolerant. Genotypes with high salt tolerance usually had poor growth potential under control conditions. This suggests that the morphological and physiological response of 38 lettuce cultivars towards SS is genotype dependent. Identifying SS’s physiological, morphological, and biochemical attributes in lettuce may help plant-breeders develop salt-tolerant lettuce genotypes.