This study investigates the long-term catalytic performance of Prussian blue nanozymes (PBNZ) as peroxidase (POD) and catalase (CAT) mimetics to elucidate their catalytic mechanisms and lifespan. Unlike Fe₃O₄ nanozymes, which exhibit depletable POD-like activity, PBNZ shows persistent and slightly enhanced catalytic activities over prolonged use. The irreversible oxidation of PBNZ significantly promotes catalysis, leading to a self-increasing catalytic activity. The catalytic process can be initiated through either the conduction band (CB) or valence band (VB) pathways. The dual-path electron transfer mechanism explains the catalytic behavior of PBNZ, ensuring a long service life. The study also highlights the importance of surface Fe oxidation and the formation of oxygenated groups in enhancing catalytic activity. Density functional theory (DFT) calculations support the experimental findings, providing a detailed understanding of the catalytic mechanism.This study investigates the long-term catalytic performance of Prussian blue nanozymes (PBNZ) as peroxidase (POD) and catalase (CAT) mimetics to elucidate their catalytic mechanisms and lifespan. Unlike Fe₃O₄ nanozymes, which exhibit depletable POD-like activity, PBNZ shows persistent and slightly enhanced catalytic activities over prolonged use. The irreversible oxidation of PBNZ significantly promotes catalysis, leading to a self-increasing catalytic activity. The catalytic process can be initiated through either the conduction band (CB) or valence band (VB) pathways. The dual-path electron transfer mechanism explains the catalytic behavior of PBNZ, ensuring a long service life. The study also highlights the importance of surface Fe oxidation and the formation of oxygenated groups in enhancing catalytic activity. Density functional theory (DFT) calculations support the experimental findings, providing a detailed understanding of the catalytic mechanism.