Fe2O3–ZrO2 catalysts with different morphologies (nanoplates (HZNPs), nanorods (HZNRs), nanocubes (HZNCs), and nanotubes (HZNTs)) were prepared by a hydrothermal method to investigate the effect of the morphology on the catalytic performance in the Fenton-like reaction for sulfamethazine (SMT) degradation. The Fe2O3–ZrO2 catalysts were characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Brunauer–Emmett–Teller (BET) analysis. The H2O2 adsorption and the Fe2+ density sites on the Fe2O3–ZrO2 catalysts had a close relationship with the morphologies and exhibited an important effect on the ·OH formation in the Fenton-like reaction. Free ·OH radicals were the main oxidative species in the reaction, and the normalized ·OH concentration per surface area of the catalysts was 4.52, 2.24, 2.20, and 0.37 μmol/m2 for HZNPs, HZNRs, HZNCs, and HZNTs, respectively. The Fe2O3–ZrO2 catalysts with different morphologies showed good catalytic performance, and the order of SMT degradation was HZNPs > HZNRs > HZNCs > HZNTs. Total SMT removal was achieved in the Fenton-like reaction over HZNPs at pH 3.0 and 45 °C after 240 min.