Zr-based MOF has been designed as a versatile adsorbent for the simultaneous removal of both As(III) and Hg(II) species with high adsorption efficiency. The synthesis procedure has been optimized to maximize the density of binding sites by introducing defects in the Zr clusters and incorporating amino functional groups into the linkers. The accessible binding sites result in high adsorption capacities of 626.71 mg g-1 for As(III) and 4.24 mg g-1 for Hg(II), which are among the highest reported values. The robustness of the adsorption performance was evaluated in various media with complex matrices, including river water and crude natural gas. Moreover, the preferential binding sites at the metal clusters and functionalized linkers were systematically investigated to elucidate their roles in the adsorption and offer new insights into the synergistic adsorption mechanisms for high removal efficiency.