Abstract: The risk posed by antibiotics in various aquifers has attracted wide attention. This study investigated the pollution characteristics and controlling factors of antibiotics in different types of aquifers, and identified the indicator factors of antibiotic pollution in aquifers based on a total of 309 sets of samples from Songnen Plain, North China Plain, and Southwest Karst area. The concentrations of 35 antibiotics were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results show that: (1) all 35 antibiotics were detected, with karst aquifers (34 types) and North China porous aquifers (32 types) mainly containing quinolones and macrolide antibiotics, while only 6 types of antibiotics, mainly erythromycin, were detected in Northeast porous aquifers. In porous aquifers, the overall pollution in Northeast China is characterized by low concentrations (median = 2.07 ng/L, detection rate = 100%), while the pollution in North China is relatively heavy (11.76 ng/L), accounting for 49% of the spatial distribution. In the karst aquifers, the antibiotic pollution is characterized by high concentrations (37.5 ng/L) and a large spatial extent (87%). (2) The characteristic differences in antibiotic pollution between karst and porous aquifers are attributed to the hydrogeological conditions (openness and permeability), while the emission intensity of antibiotics is the primary reason for the differences between porous aquifers in different regions. (3) Cluster analysis based on correlation coefficients identified the indicator factors of antibiotics in different types of aquifers. Total organic carbon (TOC) can effectively indicate the antibiotic pollution in porous aquifers, while \mathrmNH_4^+ and \mathrmSO_4^2- reveal a positive correlation between human activities and antibiotics. Groundwater property parameters are reliable indicators of antibiotic pollution in karst aquifers, with lower antibiotic concentrations observed in alkaline and oxidizing karst water. The research results can provide scientific basis for regional prevention and control of emerging organic contaminants in groundwater.