Chrome-containing waste is the major stumbling block for the leather industry. However, in current leather manufacturing, chrome tanning is difficult to replace due to the excellent characteristics it endows on the finished leather and because Cr agents play a key role in tanning. To reduce the increasing serious chrome pollution, this study establishes a Cr-wastewater loop system (CL system) to reuse Cr effluents through high-basicity chromium agent adjusting, and the mechanisms of Cr agent with different basicities affecting the CL system were explored. The basicity of Cr agent represented the number of free hydroxyls attached to the chromium atoms, which decided the binding capacity between Cr agent and collagen. Therefore, the existence forms of Cr complexes at different basicities was investigated, and the possible binding sites of Cr 3+ ions and chrome were calculated and analyzed by molecular docking. The result emphasized that highbasicity Cr agent was effective in treating Cr wastewater. The high-basicity Cr agent balances the existing forms of Cr complexes to enhance the quality of finished leather produced by CL system. After 20 cycles of Cr-wastewater reuse, Cr 3+ concentration in effluent was lower than 5 mg/L. It suggested that CL system was capable of removing chrome ions from Cr wastewater. Afterward, by analyzing the physicochemical properties, we saw that shrinkage temperature of the wet-blue produced from CL system reached 102 °C and the tensile strength was over 13 MPa, which was even to those of traditional tanning methods and meets national standards. Meantime, the organoleptic properties such as softness and grain smoothness are comparable to those of the wet-blue leather tanned by 33% basicity Cr agent as well. Therefore, the new CL system not only reduces chrome pollution from the tanning process but also ensures the high quality of leather.