This study examined a sequential Electro-Coagulation-Anodic Oxidation (EC-AO) process, using low-cost electrodes (EC: iron/stainless steel and AO: graphite/stainless steel), as an alternative for the treatment of soluble coffee industrial effluent (a complex mixture of organic macromolecules). Process operational parameters were optimized using experimental design, ANOVA, the response surface methodology, and a constrained nonlinear optimization algorithm. Experimental results allow discussing the role of graphite electrode, the mineralization via hydroxyl radicals and chlorine species (mainly as HClO and ClO− as defined from pH conditions and equilibrium calculations). EC-AO treatment allows achieving ca. 97% decolorization, as well as 72% and 65% of COD and TOC removal, respectively, with total operation costs of 10.81 USD/m3. The Molecular Weight Distribution (MWD) analysis showed that during the EC step, contaminants with molecular weight > 30 kDa were effectively decomposed. In contrast, AO was quite efficient in the mineralization of contaminants with MW in the range of 5 to 10 kDa. A kinetic analysis of EC-AO allowed defining the operation time of ca. 160 min required to meet permissible discharge limits for soluble coffee effluents, established by Colombian legislation; and obtaining COD and TOC degradation rate laws for upcoming studies on process conceptual design. Finally, the EC-AO process yielded an oxidized (AOS = 0.687), biocompatible (BOD5/COD = 0.41) not toxic effluent. Display omitted •Integrated EC-AO process was optimized for treatment of soluble coffee effluent.•The EC-AO process allows removing: color (97%), COD (72%), and TOC (65%).•EC effectively decomposed contaminants with MW > 30 kDa.•AO was efficient in mineralization of contaminants with MW in the range of 5–10 kDa.•Acute toxicity test confirmed the biocompatibility of the treated effluent.