Mn-based catalysts have exhibited promising performance in low-temperature selective catalytic reduction of NO_x with NH₃ (NH₃-SCR). However, challenges such as H₂O- or SO₂-induced poisoning to these catalysts still remain. Herein, we report an efficient strategy to prepare the dual single-atom Ce-Ti/MnO₂ catalyst via ball-milling and calcination processes to address these issues. Ce-Ti/MnO₂ showed better catalytic performance with a higher NO conversion and enhanced H₂O- and SO₂-resistance at a low-temperature window (100–150 °C) than the MnO₂, single-atom Ce/MnO₂, and Ti/MnO₂ catalysts. The in situ infrared Fourier transform spectroscopy analysis confirmed there is no competitive adsorption between NO_x and H₂O over the Ce-Ti/MnO₂ catalyst. The calculation results showed that the synergistic interaction of the neighboring Ce-Ti dual atoms as sacrificial sites weakens the ability of the active Mn sites for binding SO₂ and H₂O but enhances their binding to NH₃. The insight obtained in this work deepens the understanding of catalysis for NH₃-SCR. The synthesis strategy developed in this work is easily scaled up to commercialization and applicable to preparing other MnO₂-based single-atom catalysts.