Sulfonamide antibiotics, such as sulfamethoxazole (SMX), are found to be pollutants mostly generated from pharmaceutical wastewater with very high detection levels. The stability of SMX in water poses potential risks to ecosystems and aquatic organisms. Thus, we have taken the initiative to remove SMX from wastewater using a metal–organic framework (MOF) based nanocomposite. Our research work presents the nanocomposite of carbon nanosheets (CNS) and HKUST-1 for the first time, which is a non-toxic and economically viable adsorbent having a good surface area. HKUST-1@CNS, for effective removal of SMX from aqueous solutions, was synthesized using a simple solvothermal process followed by calcination at elevated temperature. A detailed time-dependent adsorption study of the HKUST-1@CNS nanocomposite adsorbent discloses a high 96.1% removal efficiency in only 90 min for SMX. Significant improvements in adsorption behavior have been observed for HKUST-1@CNS compared to its parent analogues. The reaction kinetics fit the pseudo-second-order reaction and the experimental adsorption data complement the Langmuir isotherm model, indicating a chemisorption route for the adsorption. The pH of the medium plays a pivotal role in the adsorption process of SMX. The adsorption behavior of HKUST-1@CNS towards SMX remains almost unchanged even after four cycles of adsorption experiments. HKUST-1@CNS was further exposed to aqueous solutions of three other antibiotics, revealing its high adsorption efficiency towards these antibiotics. The overall results indicate the utility of HKUST-1@CNS as a potential material for wastewater treatment.