A Prosopis juliflora-seed-modified Amberlite IRA-400 Cl⁻ ion-exchange resin (hereafter denoted as SMA resin) is used for the removal of Pb²⁺ from wastewater. SEM, EDX, FT-IR, BET, XRD, and XPS analyses were used to characterize the SMA resin. Parameters such as Pb²⁺ concentration, pH, temperature, and time are optimized. The obtained results show that the SMA resin has high efficiency for the removal of Pb²⁺ (73.45%) at a concentration of 100 mg L⁻¹ and a dosage of 0.01 g at pH 6. Thermodynamic studies indicate that the adsorption was spontaneous with negative ΔH° and ΔS° values at all temperatures; pseudo-second-order kinetics and the Langmuir adsorption isotherm provided the best fit (q_max = 106 mg g⁻¹ and R² = 0.99) from 298 to 338 K. In addition, a diffusion-controlled mechanism at 298 K was observed from intra-particle studies. A desorption and recovery process has been applied successfully to the SMA adsorbent. The obtained results showed desorption of 90.7% at pH 2.5 with 86.3% recovery over six cycles. Furthermore, the DFT results suggest that all the functional groups of the SMA resin possibly bind with Pb²⁺ and, of these, the –CO group shows the highest binding energy towards Pb²⁺. Moreover, the high-efficiency removal of Pb²⁺ from synthetic wastewater using the proposed SMA resin was demonstrated to show the real-life application potential.