To explore the fate and spreading mechanism of antibiotics resistance genes (ARGs) in antibiotics wastewater system, a laboratory-scale (1.47 L) Expanded Granular Sludge Bed (EGSB) bioreactor was implemented. The operating parameters temperature (T) and hydraulic retention time (HRT) were mainly considered. This result showed the removal of ARGs and COD was asynchronous, and the recovery speed of ARGs removal was slower than that COD removal. The decreasing T was attributed to the high growth rate of ARGs host bacteria, while the shortened HRT could promote the horizontal and vertical gene transfer of ARGs in the sludge. The analysis result of potential bacterial host showed more than half of the potential host bacteria carried 2 or more ARGs and suggested an indirect mechanism of co-selection of multiple ARGs. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to investigate the functional characteristics of bacterial community. This result showed the bacterial functional genes contributed 40.41% to the abundance change of ARGs in the sludge, which was higher that of bacterial community. And the function genes of “aromatic hydrocarbon degradation”, “Replication, recombination and repair proteins” and “Flagellar assembly” were mainly correlated with the transfer of ARGs in the sludge. This study further revealed the mechanism of ARGs spread in the EGSB system, which would provide new ideas for the development of ARGs reduction technology.