Point-of-use (POU) devices with satisfactory lead (Pb2+) removal performance are urgently needed in response to recent outbreaks of lead contamination in drinking water. This study experimentally demonstrated the excellent lead removal capability of two-dimensional (2D) MoS2 nanosheets in aqueous form and as part of a layer-stacked membrane. Among all materials ever reported in the literature, MoS2 nanosheets exhibit the highest adsorption capacity (740 mg/g), and the strongest selectivity/affinity toward Pb2+ with a distribution coefficient Kd that is orders of magnitude higher than that of other lead adsorption materials (5.2 × 107 mL/g). Density functional theory (DFT) simulation was performed to complement experimental measurements and to help understand the adsorption mechanisms. The results confirmed that the cation selectivity of MoS2 follows the order Pb2+ > Cu2+ ≫ Cd2+ > Zn2+, Ni2+ > Mg2+, K+, Ca2+. The membrane formed with layer-stacked MoS2 nanosheets exhibited a high water flux (145 L/m2/h/bar), while effectively decreasing Pb2+ concentration in drinking water from a few mg/L to less than 10 μg/L. The removal capacity of the MoS2 membrane is a few orders of magnitude higher than that of other literature-reported membrane filters. Therefore, the layer-stacked MoS2 membrane has great potential for POU removal of lead from drinking water.