Understanding the physiological and molecular response of crop genotypes could be useful in eco-toxicological evaluation with cadmium (Cd) and could be a strategy to solve heavy metal contamination in agriculture. This study corroborates unique patterns of Cd accumulation and molecular mechanisms adopted by plants to acquire Cd tolerance and counteractive effects of zinc (Zn) against Cd toxicity. Two rice (Oryza sativa) genotypes (Heizhan 43 and Yinni 801) differing in cadmium tolerance and its accumulation in plant tissues were investigated hydroponically using two Cd levels [Cd10 (10 μM L-1) and Cd15 (15 μM L-1)] and two Zn levels [Zn25 (25 μM L-2) and Zn50 (50 μM L-1)] and their combinations. Cadmium toxicity rendered substantial reduction in plant height, biomass, chlorophyll contents and photosynthesis as compared to the control plants after 15 days of treatment. Supplementation of Zn evidently ameliorated Cd toxicity by minimizing the reduction in plant growth, chlorophyll contents and photosynthetic attributes (Pn, gs, Ci, and Tr). Comparatively, lower accumulation of Cd in Yinni 801 under combined treatments revealed a preferential uptake of Zn in this genotype. A cross-talk among Cd, Zn, Fe, Ca and K correlated with fluctuating gs, Ci and Tr. Both genotypes also differed in morphological alterations of cell membrane, chloroplasts and appearance of enlarged plastoglobuli along with distorted mitochondria. An increased ascorbate peroxidase activity in roots of Yinni 801 presented a defensive strategy. Relative expression of Cd and Zn ion transporter genes also confirmed the genotypic background of phenotypic divergence. The OsLCT1 and OsHMA2 expression was significant in Heizhan 43, indicating possible translocation of Cd from shoot to grains contrary to Yinni 801, which accumulated Cd in shoot and showed stunted growth. Zn supplementation promises tolerance to Cd in Yinni 801 by differential expression of putative genes for Cd translocation with minimum ultrastructural modifications by maintaining physiological functions in contrast to Heizhan 43.