This study comprehensively investigated the comparative acute toxicities, degradation, transcriptome, and oxidative stress induction of fenpropathrin (FEN) and its main metabolite 3-phenoxybenzoic acid (3-PBA)in soil-earthworm microcosms. FEN degradation half-life ranged from 19.09 to 28.52 days, and the peak-shaped trends of 3-PBA were also observed in different soil types. The LC50 values of FEN and 3-PBA were 12.75 and 7.49 μg/cm2, respectively, suggesting that 3-PBA was more toxic to earthworms. Furthermore, the sub-lethal toxicities indicated that 3-PBA exerted more prominent alterations in protein content, enzyme activity, lipid peroxidation, and oxidative stress in earthworms. Additionally, integrated biomarker response evaluations indicated that 3-PBA induced more prominent sub-lethal toxicity in earthworms than FEN. Finally, exposure to FEN and 3-PBA resulted in distinct differentially expressed genes (DEGs) in earthworms. Enrichment analysis revealed that these DEGs were predominantly enriched in purine metabolism and bile secretion pathways in earthworms. Moreover, the p53 signaling pathway, cell cycle, DNA replication, drug metabolism, and pyrimidine metabolism were also enriched in earthworms after exposure to FEN and 3-PBA. These results suggested that FEN and 3-PBA induced varying toxicities in earthworms. This study highlighted the systemic differences in the toxicities, degradation, transcriptome, and oxidative stress induction between FEN and 3-PBA in soil-earthworm microcosms. Our findings could be used for a comprehensive risk assessment of FEN and 3-PBA in the soil ecosystem.