Peroxyacetic acid (PAA)-based advanced oxidation processes (AOPs) have attracted much attention in wastewater treatment by reason of high selectivity, long half-life reactive oxygen species (ROS), and wider applicability. In this study, cobalt ferrite (CoFe₂O₄) was applied to activate PAA for the removal of ofloxacin (OFX). The degradation of OFX could reach 83.0% via the CoFe₂O₄/PAA system under neutral conditions. The low concentration of co-existing anions and organic matter displayed negligible influence on OFX removal. The contributions of hydroxyl radicals (·OH), organic radicals (R-O·), and other reactive species to OFX degradation in CoFe₂O₄/PAA were systematically evaluated. Organic radicals (especially CH₃C(O)OO·) and singlet oxygen (¹O₂) were verified to be the main reactive species leading to OFX destruction. The Co(II)/Co(III) redox cycle occurring on the surface of CoFe₂O₄ played a significant role in PAA activation. The catalytic performance of CoFe₂O₄ remained above 80% after five cycles. Furthermore, the ecotoxicity of OFX was reduced after treatment with the CoFe₂O₄/PAA system. This study will facilitate further research and development of the CoFe₂O₄/PAA system as a new strategy for wastewater treatment.