Arsenic (As) accumulation in rice is a principal route of As exposure for rice based population. We have tested physiochemical and molecular parameters together to identify low As accumulating rice cultivars with normal growth and vigor. The present study examined potential toxicity caused by arsenate (AsV) among four rice cultivars tested that varied with respect to accumulation of total arsenic, arsenite (AsIII) and their differential translocation rate which had deleterious impact on growth and metabolism. Intracellular homeostasis of rice cultivars viz., TN-1, IR-64, IR-20 and Tulaipanji was hampered by 21 days long As(V) treatment due to generation of reactive oxygen species (ROS) and inadequate activity of catalase (CAT; EC 220.127.116.11). Upregulation of oxidative stress markers viz., H2O2, proline and MDA along with alteration in enzymatic antioxidants profile were conspicuously pronounced in cv. Tulaipanji while cv. TN-1 was least affected under As(V) challenged environment. In addition to that genomic template stability and band sharing indices were qualitatively measured by DNA profiling of all tested cultivars treated with 25 μM, 50 μM, and 75 μM As(V). In rice cv. Tulaipanji genetic polymorphism was significantly detected with the application of random amplified polymorphic DNA (RAPD) tool and characterized as susceptible cultivar of As compared to cvs. TN-1, IR-64 and IR-20 that is in correlation with data obtained from cluster analysis. Hence, identified As tolerant cultivars viz., TN-1, IR64 and IR-20 especially TN-1 could be used in As contaminated agricultural field after appropriate field trial. This study could help to gather information regarding cultivar-specific tolerance strategy to avoid pollutant induced toxicity. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.