The application of promising g-C3N4 has been limited by poor photogenerated electron-hole separation and limited absorption for visible light. Sulfamethoxazole (SMX) is a typical antibiotic drug that is used worldwide and hard to be disposed through conventional wastewater treatment methods. Herein, S-scheme Fe2O3/g-C3N4 heterojunction was successfully prepared via a facile one-step sintering method and applied to photodegrade SMX under visible light irradiation. The integration of Fe2O3 and g-C3N4 shows superior charge separation and light absorption ability. As a result, the removal efficiency of 11 wt% Fe2O3/g-C3N4 reaches to 99.2% within 30 min, which is visibly higher than 59.5% of pure g-C3N4. ·O2− and ·OH are demonstrated to be the predominant active species for SMX photodegradation, and the possible degradation pathway is also proposed based on electronic band structure of Fe2O3/g-C3N4 heterojunction. This study presents a facile construction of g-C3N4 based S-scheme photocatalyst and offers an environmentally friendly approach to effectively remove organic pollutants using renewable solar energy.