In this work, a novel approach coupling a heterogeneous weak magnetic field (WMF) with the CoFe2O4/peroxyacetic acid (PAA) system was employed to enhance the degradation of sulfamethoxazole (SMX). Under the optimized conditions of 50 mT WMF, 0.1 g/L CoFe2O4, 0.2 mM PAA, and initial pH 6.0, a complete degradation of 10 μM SMX was achieved in 25 min, exhibiting a high synergistic coefficient of 1.61. This result indicates a significant synergistic effect among WMF, CoFe2O4, and PAA in effectively degrading SMX. The introduction of WMF did not alter the pH application range of the CoFe2O4/PAA system. Furthermore, the degradation efficiency of SMX by the CoFe2O4/PAA/WMF system was significantly reduced in the presence of humic acid (HA) and bicarbonate ions (HCO3−), while chloride ions (Cl−) exhibited a minor inhibitory effect. Quenching experiments and electron paramagnetic resonance (EPR) analysis reveal that WMF did not alter the types of reactive oxygen species (ROS) generated in the CoFe2O4/PAA system. The degradation of SMX in the CoFe2O4/PAA/WMF system involved both radical (CH3C(O)O∙ and CH3C(O)OO∙) and non-radical (1O2) oxidation pathways, driven by the redox cycling between ≡Co2+/≡Co3+ and PAA, as well as the rapid adsorption and transformation of oxygen (O2) at oxygen vacancies (OV), respectively. The presence of WMF enhanced the utilization of PAA by CoFe2O4 by improving the convection and mass transport in the solution, facilitating the formation of superoxide anion (O2∙−) and supplemented lattice oxygen (O2−) through the directional migration of paramagnetic O2 towards the CoFe2O4 surface, thus significantly promoting ROS formation. Additionally, the degradation pathways of SMX in the CoFe2O4/PAA/WMF system were proposed based on density functional theory (DFT) calculations and the detected transformation products (TPs). The toxicity of SMX was effectively reduced, as verified by predictions from the Ecological Structure-Activity Relationship Model (ECOSAR) procedure. The excellent catalytic performance, reusability, and effective degradation of various organic pollutants demonstrated by the CoFe2O4/PAA/WMF system suggest its potential as a promising strategy for water treatment.