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The increasing occurrence of active pharmaceutical ingredients (APIs) in water systems coupled with their recalcitrance to conventional water treatment methods calls for research into more eco-friendly and cost-effective curbing media. Mesoporous cassava peel activated carbon (CPAC) was prepared under conditions derived from optimizing the surface area and yield with the temperature and holding time as the model inputs using the response surface methodology. The sequestration potential and mechanisms of the resultant activated carbon (AC) for active pharmaceutical ingredients from wastewater were studied using batch experiments. The CPAC adsorption kinetics and isothermal mechanisms for the three pharmaceuticals (carbamazepine (CBZ), clarithromycin (CLN), and trimethoprim (TRM)) were studied in both wastewater and Milli-Q water. The API concentrations were measured using liquid chromatography coupled to a mass spectrometer (LC-MS) system. The maximum removal efficiencies were 86.00, 58.00, and 68.50% for CBZ, CLN, and TRM for wastewater, which were less than those from the Milli-Q water at 94.25, 73.50, and 84.5%, respectively. The sorption process for the CLN was better explained by the Freundlich model, whereas the CBZ and TRM adsorption processes could suitably be explained by both the Langmuir and Freundlich models. At an initial concentration of 20 mgL−1 for all APIs and a CPAC dosage of 2.0 gL−1, the maximum adsorption capacities were 25.907, 84.034, and 1.487 mgg−1 for CBZ, TRM, and CLN, respectively. These results demonstrated the potential of CPAC to remove APIs from water, with its sequestration potential being more exhibited after the removal of the organic matter owing to the lower competition for active sites by the APIs. Additionally, positive adsorbates were better removed than negatively charged adsorbates due to the dominance of anions in the cassava peel lattice.