The distribution pattern of metals as active centers on a substrate can influence the peroxymonosulfate (PMS) activation and contaminants degradation. Herein, atomic layer deposition is applied to prepare Cu single atom (SA-Cu), cluster (C-Cu), and film (F-Cu) decorated MXene catalysts by regulating the number of deposition cycles. In comparison with SA-Cu-MXene (adsorption energy (E_ads) = −4.236 eV) and F-Cu-MXene (E_ads = −3.548 eV), PMS is shown to adsorb preferably on the C-Cu-MXene surface for activation (E_ads = −5.435 eV), realizing higher utilization efficiency. More SO4^·− are generated in C-Cu-MXene/PMS system with steady-state concentration and 1–3 orders of magnitude higher than those in the SA-Cu-MXene and F-Cu-MXene activated PMS systems. Particularly, the contribution of SO4^·− oxidation to sulfamethoxazole (SMX) degradation followed the order, C-Cu-MXene (97.3%) > SA-Cu-MXene (90.4%) > F-Cu-MXene (71.9%), realizing the larger SMX degradation rate in the C-Cu-MXene/PMS system with the degradation rate constants (k) at 0.0485 min⁻¹. Additionally, SMX degradation routes in C-Cu-MXene/PMS system are found with fewer toxic intermediates. Through this work, we highlighted the importance of guided design of heterogeneous catalysts in the PMS system. Appropriate metal distribution patterns need to be selected according to the actual water treatment demand. Metal sites could be then fully utilized to produce specific active species to improve the utilization efficiency of the oxidants.