Within human-influenced landscapes, pesticides cooccur with a variety of antibiotic stressors. However, the relationship between pesticides removal process and antibiotic resistance gene variation are not well understood. This study explored pesticide (topramezone, TPZ) and antibiotic (polymyxin E, PME) co-contamination using liquid chromatography-tandem mass spectrometry (LC-MS/MS), bacterial-16 S rRNA sequencing and high-throughput quantitative polymerase chain reaction (HT-qPCR) in a soil-earthworm-maize system. After incubating soil for 28 days with TPZ and PME (10 mg kg−1 dry weight), earthworm weight-gain, mortality rates, and maize plant weight-gain only differed slightly, but height-gain significantly decreased. PME significantly increased TPZ-removal in the soil. Accumulation of TPZ in earthworm's tissues may pose potential risks in the food chain. Combined pollution altered the microbial community structure and increased the abundance of functional microorganisms involved in aromatic compound degradation. Furthermore, maize rhizosphere can raise resistance genes, however earthworms can reduce resistance genes. Co-contamination increased absolute abundance of mobile genetic elements (MGEs) in bulk-soil samples, antibiotic resistance genes (ARGs) in skin samples and number of ARGs in bulk-soil samples, while decreased absolute abundance of transposase gene in bulk-soil samples and number of ARGs in rhizosphere-soil samples. Potential hosts harbouring ARGs may be associated with the antagonistic effect during resistance and detoxification of TPZ and PMB co-occurrence. These findings provide insights into the mechanism underlining pesticide removal regarding occurrence of ARGs in maize agroecosystem.