Single-atom catalysts (SACs) have emerged as a promising frontier in Fenton-like processes. However, optimizing their isolated and dispersed active sites remains a major challenge. Herein, a Mn-modulated dual-Fe-site catalyst (FeMn-NC) featuring both Fe single atoms and Fe nanoclusters was developed. Mn incorporation promoted the formation of Fe nanoclusters composed of Fe⁰ and Fe_1.8Mn_1.2C species. The catalyst achieved 97.1% tetracycline (TC) degradation via peroxymonosulfate (PMS) activation, with a reaction rate constant (k) of 0.1152 min⁻¹, arising from the synergistic interplay between Fe single atoms and Fe nanoclusters. Mechanistically, Fe single atoms dominated the non-radical pathway, whereas Fe nanoclusters enhanced electron transfer and introduced a complementary radical route. Density functional theory (DFT) calculations revealed that the coexistence of Fe single atoms and Fe nanoclusters optimized charge distribution and the Fe d-band center, thereby enhancing electron delocalization and promoting PMS adsorption, O–O bond activation, and interfacial Bader charge transfer. Additionally, Fukui function calculation, intermediate products analysis, and wheat germination assays confirmed the reduced environmental toxicity of pollutants after catalytic degradation. This work provides new insights into the rational design of SACs with multiple active sites for the efficient catalytic PMS activation.