The present investigation assesses the physiological and biochemical responses of pomegranate plants (Punica granatumL.) to increased concentrations of hexavalent chromium (Cr6+) after 150 days of growth under in vivo conditions. The tested cultivars (cvs) were ‘Wonderful’, ‘Acco’, and ‘Ermioni’. The aim of this research was to study accumulation of total Cr and its distribution in leaves and roots, as well as its effects on growth, total chlorophyll (a + b), carotenoids, porphyrins, phenols, flavonoids, and antioxidant capacity (FRAP assay) of leaves. The measured parameters where the total fresh weight of leaves and roots; the total Cr concentration of leaves and roots; and the chlorophyll, carotenoids, porphyrins, and carbohydrate concentration. Furthermore, total phenols, flavonoids, and FRAP were measured. The results indicated that addition of Cr6+in the nutrient solution caused augmentation of chromium concentration in roots and leaves of pomegranate plants. Total Cr in roots was 11–16 times greater than in leaves. Concerning porphyrin concentration, ‘Wonderful’ was the most negatively affected cultivar. Total phenols, flavonoids, and FRAP values increased due to Cr6+treatment. Chromium concentration of 20 and 40 mg L−1increased significantly chromium level of leaves and roots in pomegranate plants. ‘Ermioni’ accumulates less Cr in leaves, in comparison with the other cvs, and has greater chlorophyll, phenol, and flavonoid concentration and FRAP value. ‘Ermioni’ could be considered a more tolerant cv to Cr6+toxicity compared with ‘Wonderful’ and ‘Acco’.