Intensive use of antibiotics affects biogeochemical cycles and stimulates the evolution of antibiotic resistance, thus threatening global health and social development. The spatiotemporal distributions of antibiotics in single aqueous matrices have been widely documented; however, their occurrence in surface–groundwater systems has received less attention, especially in arid regions that usually have fragile ecosystems. Therefore, we investigated the occurrence of thirty-one antibiotics in the surface water and adjacent groundwater in the Xinjiang Uygur Autonomous Region, China. The results showed that the total concentrations of detected antibiotics varied from 17.37 to 84.09 ng L⁻¹ and from 16.38 to 277.41 ng L⁻¹ in surface and groundwater, respectively. The median concentration of antibiotics showed the pattern of norfloxacin (4.86 ng L⁻¹) > ciprofloxacin (3.93 ng L⁻¹) > pefloxacin (3.39 ng L⁻¹) in surface water; whereas in groundwater, this was in the order of pefloxacin (6.30 ng L⁻¹) > norfloxacin (4.33 ng L⁻¹) > ciprofloxacin (2.68 ng L⁻¹). Heatmap analysis indicated that vertical infiltration had limited effects on antibiotic exchange in surface–ground water systems because of the high potential evaporation and low water storage. Redundancy analysis suggested that the oxidation–reduction potential (p < 0.01) and dissolved oxygen (p < 0.05) jointly affected the distribution of antibiotics in surface water. Ecological risk assessment showed that antibiotics in 98.9% of surface water and 99.1% of groundwater did not pose significant risks to aquatic species. The findings of this study will help develop effective mitigation strategies for antibiotics in aquatic environments.