Oxytetracycline (OTC) is frequently detected in groundwater and soil, posing substantial risks to the subsurface environment via persistence, phytotoxicity, changing bacterial communities, and antibiotic resistance. In situ chemical oxidation (ISCO) is one of the best alternatives for removing OTC from groundwater. However, its feasibility has rarely been investigated using columns for which optimal conditions can be obtained for practical applications. Thus, a system consisting of oxygen-doped graphitic carbon nitride (OgCN) and peroxymonosulfate (PMS) (OgCN/PMS) was tested for OTC removal using continuous-flow experiments with columns packed with sand and glass beads (GBs). The sand column exhibited better adsorption and degradation of OTC than the GB column in pulse injection experiments, regardless of whether OgCN was packed. Additional experiments were performed using a column saturated with the OTC solution and another filled with deionized water to simulate ISCO, using GB as the medium, to evaluate the net OTC removal by catalytic oxidation, excluding adsorption. Performance improved with increased OgCN packing, PMS dosage, retention time, and pH. Anions slightly affected the performance due to scavenging and propagation of radicals. These findings indicate the high potential of OgCN/PMS for ISCO and the usefulness of column experiments in field applications.