The presence of antimicrobial sulfa chemicals in water is becoming a more serious problem and action must be taken to create an effective decontamination process for wastewater treatment. In this way, current thinking has focused on removing sulfa drugs as broad-spectrum antimicrobials from water by metal organic framework ((Cu&Co)-benzenetricarboxylate, M−BTC) bound within the amberlite polymer. Here, M(Cu&Co)-BTC is synthesized and incorporated within amberlite polymer in a single step. Moreover, the adsorptive capacities of the various sulfa drugs (sulfamethazine and sulphanilamide) were investigated using M−BTC@amberlite compounds for the first time. The adsorption efficiency of the sulfa drugs was monitored (higher performance for sulfamethazine rather than sulfanilamide), and the adsorption uptake was reached 99 % within about 60 min. The adsorption isotherms were best fitted using the Langmuir and pseudo-second-order model, individually. The greatest potencies for Cu-BTC@amberlite and Co-BTC@amberlite were 205 and 306 mg/g for sulfamethazine and 326 and 488 mg/g for sulfanilamide, separately. By incorporating Co-BTC within amberlite, the absorption capacity of sulfamethazine and sulfanilamide was extended by 1.72 and 1.83 times, respectively, while incorporation of Cu-BTC within amberlite, the adsorption capacity of sulfamethazine and sulfanilamide was extended by 2.56 and 2.73 times, respectively. The attached MOFs with polymer showed very high reusability and their efficacy in uptake of sulfamethazine and sulfanilamide diminished by 14.8–15.9 % and 11.3–12.7 %, separately, after five sequential adsorption cycles. Hence, in agreement with the adsorption result, a conceivable tool is proposed. The sulfa drug adsorption performed on a range of BTC-MOFs with diverse physicochemical properties and point-by-point characterization confirmed that the highest adsorption capacity of MOFs is achieved through bi-bi interaction; H-bonding between NH sites of sulfa drug particles and O sites of carboxyl units within MOFs. In scale-up, M−BTC@amberlite has demonstrated remarkable reusability, which is enticing for potential applications in the adsorption of sulfa drugs from wastewater.