The treatment of tannery wastewater is a complex environmental challenge. These effluents have high loads of total suspended solids (TSS) and, especially, sulfides, pollutants that require advanced technologies due to their toxicity and difficulty in removal. This study presents and evaluates an integrated electrocoagulation (EC) and ozonation (O3) system as an alternative for the comprehensive treatment of this effluent. In the EC stage, it was optimized using the response surface methodology (RSM) with a 3k factorial design, using current intensity (I) and treatment time (t) as factors to maximize TSS removal. The EC results demonstrated high TSS removal efficiency, reaching 97.91% under optimal conditions (p < 0.05), which significantly facilitates subsequent treatment. The most critical finding of the study lies in the ineffectiveness of EC for dissolved contaminants: the removal of sulfides was extremely limited, with an efficiency of only 4.2%. In contrast, the subsequent ozonation stage achieved more than 99% elimination of sulfides using a dose of 12 g h-1 of ozone after 20 minutes of reaction. This result justifies the need for an integrated system, where EC handles the load of solids (TSS) and other contaminants and ozonation performs the essential chemical oxidation of sulfides. The operating cost of the combined EC–O3 treatment was determined to be US$ 0.707 m-3, demonstrating the economic viability of the technology. The results confirm that the EC–O3 system is a synergistic solution for the environmental management of tannery wastewater, enabling compliance with maximum permissible limits.