The current work aimed to develop a sustainable and eco-friendly method for treating leather industry wastewater using Azadirachta indica (neem) leaf extract and copper nanoparticles (Cu NPs) synthesized through a green synthesis approach from the same plant source. Three treatment phases were designed: (i) characterizing untreated (pre-treated) wastewater, (ii) treating with A. indica leaf extract at a 10:200 mL ratio, and (iii) treating with Cu NPs at 0.5 g/L in addition to A. indica extract. Key water quality parameters such as pH, chemical oxygen demand (COD), biological oxygen demand (BOD), total dissolved solids (TDS), total suspended solids (TSS), and chromium (Cr) concentration were analyzed for each case and compared to the Pakistan Environmental Quality Standards (PEQS). The results revealed considerable increases in water quality following treatment. Treatment with A. indica extract alone resulted in significant COD, BOD, TDS, TSS, and pH reductions, whereas the addition of Cu NPs increased removal efficiency even more. COD dropped from 510 to 40 mg L−1, BOD from 145 to 116 mg L−1, TDS from 3829 to 499 mg L−1, and pH fell from 9.0 to 6.5, bringing the treated water closer to regulatory norms. Furthermore, the maximum Cr removal was 98%, equivalent to an adsorption capacity of 49 mg/g at an equilibrium pH of 5, a contact period of 2 h, and a Cu NPs dose of 0.5 g L−1. To better understand the adsorption behavior and process, equilibrium data were fitted to several isotherm models, with the Langmuir isotherm model providing the best fit, implying monolayer chemisorption as the dominant mechanism for Cr removal. This green treatment strategy, which combines plant-based bioactive chemicals with metal nanoparticles, provides a cost-effective and environmentally friendly option for reducing pollution from the leather industry. The study proposes implementing this technology on an industrial scale for optimal wastewater management and environmental preservation.