Intensive use of antibiotics promotes the occurrence and development of antibiotic resistance. Antibiotic resistance genes (ARGs) enter water environments from human and animal sources. Groundwater serves as an important water supply, while the profiles and risk of ARGs in groundwater remain unknown. The abundance and profiles of ARGs in 11 domestic wells in the Maozhou River basin of Shenzhen City were analyzed by high-throughput qPCR. The results showed that a total of 141 ARGs and 8 mobile genetic elements (MGEs) were detected, of which the genes corresponding resistance to sulfonamides, multidrugs, and aminoglycosides were the most abundant. In each well, the number of detected ARGs and MGEs ranged from 48 to 89, with an average of 68. When normalized by the abundance of 16S rRNA genes, it was found that each bacterium carried at least one ARG in the groundwater of W7, W8, and W10, while in W11, each bacterium carried at least four ARGs. Clinically relevant ARGs that code for resistance to glycopeptide (, , , and ), -lactams ( and ), or chloramphenicol () were found in groundwater. In addition, the abundance of sulfonamides, multidrugs, aminoglycosides, -lactam, and chloramphenicol resistance genes were positively correlated with the abundance of MGEs (<0.01), suggesting that MGEs may promote the spread of ARGs in groundwater.