Drought and salinity stresses are persistent threat to field crops and are frequently mentioned as major constraints on worldwide agricultural productivity. Moreover, their severity and frequency are predicted to rise in the near future. Therefore, in the present study we investigated the mechanisms underlying plant responses to drought (5, 10 and 15% polyethylene glycol, PEG-6000), salinity (50, 100, and 150 mM NaCl), and their combination, particularly at the seed germination stage, in terms of photosynthesis and antioxidant activity, in four soybean cultivars, viz., PI408105A (PI5A), PI567731 (PI31), PI567690 (PI90), and PI416937 (PI37). Results showed that seed germination was enhanced by 10% PEG and decreased by 15% PEG treatments compared to the control, while seed germination was drastically decreased under all levels of NaCl treatment. Furthermore, combined drought and salinity treatment reduced plant height and root length, shoot and root total weights, and relative water content compared with that of control. However, the reductions were not similar among the varieties, and definite growth retardations were observed in cultivar PI5A under drought and in PI37 under salinity. In addition, all treatments resulted in substantially reduced contents of chlorophyll pigment, anthocyanin, and chlorophyll fluorescence; and increased lipid peroxidation, electrolyte leakage, and non-photochemical quenching in all varieties of soybean as compared to the control plants. However, proline, amino acids, sugars, and secondary metabolites were increased with the drought and salinity stresses alone. Moreover, the reactive oxygen species accumulation was accompanied by improved enzymatic antioxidant activity, such as that of superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase. However, the enhancement was most noticeable in PI31 and PI90 under both treatments. In conclusion, the cultivar PI31 has efficient drought and salinity stress tolerance mechanisms, as illustrated by its superior photosynthesis, osmolyte accumulation, antioxidative enzyme activity, and secondary metabolite regulation, compared to the other cultivars, when stressed.