With the continuous increase in shrimp (Litopenaeus vannamei) aquaculture production, the widespread use of antibiotics as a means of preventing and treating diseases has adversely affected the environment, animal health and symbiotic microorganisms in gut environments. At the same time, antibiotic resistance genes (ARGs) are widespread in aquaculture and pose a great threat to aquatic organisms and humans. Therefore, in the present study, the occurrence and distribution of 17 antibiotics, ARGs and mobile genetic elements (MGEs) were detected in the guts of shrimp collected from 12 coastal regions of China. The results showed that sulfadiazine, ciprofloxacin and norfloxacin were detectable in the guts of L. vannamei at all sampling sites. Sul1, sul2, floR and intI-1 were also detected in the guts of L. vannamei at all sampling sites. The total relative abundances of ARGs and MGEs were significantly positively correlated according to Pearson correlation analysis. Sulfonamide resistance genes (sul1 and sul2) were significantly positively correlated with intI-1. These results indicated that MGEs could increase the risk of horizontal gene transfer of ARGs in a gut environment. MGEs are the most important factors promoting the spread of ARGs. Correlation analysis showed that sulfadiazine was significantly positively correlated with sul1 and sul2 and that fluoroquinolone antibiotics were significantly positively correlated with floR, indicating that antibiotics could induce the production of ARGs. Network analysis indicated that Iamia and Alkaliphilus species may harbor the most antibiotic resistance genes, and these bacteria were closely related to the proliferation and spread of ARGs in a gut environment. Antibiotic use and the spread of ARGs in mariculture systems may have negative effects on shrimp and human health. The use of antibiotics should be strictly regulated to control contaminants in mariculture systems, including pathogens and ARGs, thereby reducing potential risks to human health.