Excessive zinc powder consumption and low cadmium content in purified cadmium removal residues are persistent challenges in cadmium removal from zinc sulfate solution via zinc powder replacement. The primary cause is the reduced reactivity of zinc powder due to encapsulation by product layers. To address this, a novel two-stage countercurrent replacement method with mechanical activation was proposed. This method involves adding low-coefficient zinc powder in the first stage to facilitate cadmium enrichment and high-coefficient zinc powder in the second stage to achieve the desired cadmium removal from zinc sulfate solutions, meeting solution purification standards. Experimental results show that, under optimal conditions (total zinc powder addition coefficient of 1.02, reaction temperature of 60 °C, and reaction time of 60 min), using a primary zinc powder addition coefficient of 0.9 and a secondary zinc powder addition coefficient of 1.2 reduced cadmium concentration in the solution from 1 530 mg/L to 60-70 mg/L after the first stage. This process enriched the cadmium content in the primary purification residue to 81.54%, with zinc content below 10%. Following secondary purification, cadmium concentration in the solution further decreased to 2 mg/L to 5 mg/L, while the purification residue contained 16.09% cadmium and 56.04% zinc. Phase analysis revealed that the primary purification residue predominantly consisted of elemental cadmium, whereas the secondary residue contained unreacted zinc and some elemental cadmium. Compared with traditional primary purification methods, the introduction of fluid shear stress and mechanical activation effectively disrupted the encapsulation layer on zinc powder surfaces, eliminating the the wrapping effect, enhancing zinc powder utilization efficiency, reducing consumption, and increasing cadmium content in the purification residues.