Improving the photosensitization efficiency represents a critical challenge in photodynamic therapy (PDT) research. While cyanines exhibit potential as photosensitizers (PSs) due to their large extinction coefficients and excellent biocompatibility, the inherent limitations in intersystem crossing severely affect therapeutic efficacy. Herein, we proposed a bottom-up magnetically enhanced photodynamic therapy (magneto-PDT) paradigm employing fluorobenzene-substituted pentamethine cyanine as type-I reactive oxygen species generators. Based on the radical pair mechanism and magnetic field effect, the notable difference in g-factors (Δg) between PSs and oxyradicals enabled magnetically responsive amplification of Cy5-3,4,5-3F-mediated hydroxyl radical (•OH) and superoxide anion radical (O) production, achieving maximum yield enhancements of 66.9 and 28.0% respectively at 500 mT. This magnetically augmented oxyradicals generation exhibited universal cytotoxicity superiority over conventional PDT protocols in various cancer cell models. Notably, the semi-inhibitory concentration (IC) of murine mammary carcinoma 4T1 cells demonstrated a remarkable reduction under both normoxic and hypoxic conditions, with the most pronounced decrease observed in normoxia from 0.91 μM (PDT alone) to 0.38 μM (magneto-PDT). The significantly magneto-enhanced therapeutic performance effectively inhibited orthotopic tumor growth. This magneto-PDT paradigm established a novel strategy for manipulating spin-dependent photosensitization processes in biological applications.