The efficiency of Azadirachta indica (neem leaves) on the removal of Pb(II) ions by adsorption from aqueous solution was investigated in this study. The efficiency of these leaves (without chemical or thermal treatment) for the adsorption of Pb(II) ions has not previously been reported. Batch experiments were performed to study the effect of the particle size, pH, adsorbent dose, contact time, initial Pb(II) ion concentration, and temperature. The maximum removal of 93.5% was achieved from an original Pb(II) ion solution concentration of 50 mg/L after 40 min, at pH 7, with 0.60 g of an adsorbent dose. The maximum adsorption capacity recorded was 39.7 mg/g. The adsorption process was also studied by examining Langmuir, Freundlich, Temkin isotherm, and Dubinin–Radushkevich (D-R) isotherm models. The results revealed that the adsorption system follows the pseudo-second-order model and fitted the Freundlich model. Several thermodynamic factors, namely, the standard free energy (∆G°), enthalpy (∆H°), and entropy (∆S°) changes, were also calculated. The results demonstrated that the adsorption is a spontaneous, physical, and exothermic process. The surface area, pore size, and volume of adsorbent particles were measured and presented using a surface area analyzer (BET); the morphology was scanned and presented with the scanning electron microscope technique (SEM); and the functional groups were investigated using μ-FTIR.