Combinations of metal(loid) contamination and antibiotics are considered to increase the abundance of resistance genes in the environment, whereas the combined effect of metal(loid)s and antibiotics on microbial communities and antibiotic resistance genes (ARGs) in the gut of soil fauna remains unknown. We investigated herein the alteration of ARGs and the gut microbial communities after the earthworm Metaphire sieboldi was exposed to arsenate and/or sulfamethoxazole using high-throughput quantitative PCR and Illumina sequencing analysis. Arsenic accumulation in the body tissues of arsenic-exposed earthworms exerted a significant inhibition on growth and survival. The synergistic interactions of arsenic and sulfamethoxazole increased significantly the incidence of ARGs and mobile genetic elements in the earthworm gut microbiota. In addition, co-exposure to arsenic and sulfamethoxazole altered the structure of the gut microbial communities, and the changes correlated with ARG profiles of the gut microbiota. Our results indicate that the gut of soil fauna is a neglected hotspot of antibiotic resistance.