BACKGROUNDAcetaminophen, also known as paracetamol, has been notably detected in aquatic environments, including wastewater, surface water and drinking water, causing significant concern within the scientific and environmental research communities. This study focuses on two main objectives: (i) optimizing corn cob‐based activated carbon (CCAC) through response surface methodology for the adsorption of acetaminophen and (ii) simulating the acetaminophen adsorption process using the polymath mass transfer (PMT) model.RESULTSThe optimized CCAC was prepared via physiochemical activation under microwave radiation (265 W power) for 6 min, with a KOH impregnation ratio of 0.50 g g−1. This process resulted in a high Brunauer–Emmett–Teller surface area of 976.29 m2 g−1, accompanied by a corresponding pore volume of 0.39 cm3 g−1 and a pore diameter of 2.38 nm. The adsorption study, employing differential initial concentrations (ranging from 5 to 30 mg L−1) of acetaminophen, revealed a substantial adsorption capacity of 22.43 mg g−1 (74.77%) at 30 °C and 20.74 mg g−1 (69.13%) at pH 6. The PMT model indicated an adsorption capacity (Qm) of 21.14 mg g−1, with an error of 5.75%, demonstrating high precision compared to the experimental result. Additionally, the calculated R2 values equal to or above 0.90 indicated strong agreement between the PMT model and experimental data.CONCLUSIONThus, applying the PMT model proved to be economical and cost‐effective, providing accurate predictions on surface area during adsorption performance compared to the time‐consuming and costly process of conducting characterizations. © 2024 Society of Chemical Industry (SCI).