This study investigated the impact and regulatory mechanisms of soil active components—montmorillonite (MMT), humic acid (HA), and their composite (MMT-HA) on the microbial degradation of nicosulfuron using the highly efficient degradation fungus Talaromyces flavus LZM1. Advanced analytical techniques, including scanning electron microscopy coupled with X-ray energy-dispersive spectroscopy (SEM-EDS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF), were employed to systematically characterize the degradation process. The results demonstrated that individual or composite soil components (MMT, HA, or MMT-HA) enhanced microbial degradation activity by providing microbial colonization surfaces or energy metabolism substrates, which altered fungal hyphal morphology and shifted nicosulfuron degradation kinetics from first-order to zero-order. This not only enhanced microbial adaptability to high-pollution stress but also reduced the phase-transport potential and secondary toxicity of key degradation products such as 2-amino-4,6- dimethoxypyrimidine (ADMP). Furthermore, interactions between soil active components and microorganisms led to changes in nicosulfuron degradation pathways and product profiles. The results revealed that soil components stimulated microbial production of antioxidative metabolites (e.g., orsellinic acid) to counteract oxidative stress, while the formation of orsellinic acid conjugates further reduced ADMP accumulation. Comparatively, MMT significantly inhibited hydroxylation product generation, whereas HA promoted alcoholysis product formation. These findings deepen the mechanistic understanding of nicosulfuron biodegradation and provide a scientific basis for optimizing microbial degradation technologies in agricultural soils contaminated with sulfonylurea herbicides.