This study was conducted to determine the tolerance of safflower (Carthamus tinctorius L.) cultivars (Dincer, Remzibey-05, and Yenice) against salt stress based on some physiological and biochemical parameters at the vegetative stage. Eighteen-day-old plants were subjected to salt stress [0 (control), 75, 150, 225, and 300 mM NaCl concentrations] for 12 days, which led to a significant decrease in growth parameters (stem growth, fresh weight, and relative water content) and the photosynthetic pigment contents of the safflower cultivars. The photochemical activities of photosystem II of the cultivars were negatively affected by salinity, especially at the highest concentration (300 mM). Salt stress decreased K+ content and K+/Na+ ratio while it increased Na+ content. Malondialdehyde and free proline contents in the leaves of cultivars increased gradually in proportion to the increase of NaCl concentration. Analysis of antioxidant enzyme activities showed that these enzymes responded differently to the NaCl concentrations. Dincer, with higher antioxidant enzyme activities, had a more effective response than the other cultivars. Considering growth and biochemical and chlorophyll fluorescence parameters with the endogenous defense system, Dincer had a higher withstanding capacity against salinity than the other cultivars.