Due to rapid socioeconomic development, antibiotic pollution and heavy metal pollution are receiving increasing amounts of attention. Both antibiotics and heavy metals in the environment are persistent and toxic, and the interactions between the pollutants create potential long-term hazards for the ecological environment and human health as mixed pollutants. In this study, the surface water of the Yitong River in Changchun was used as the research object, and the hazards associated with antibiotics and heavy metals in the surface water were assessed by analyzing the spatial and temporal distribution characteristics of antibiotics and heavy metals and by using ecological risk assessment and human health risk assessment models. The results showed that ofloxacin (OFL) and norfloxacin (NOR) varied seasonally according to the seasonal climate, with total concentrations ranging from 17.65 to 902.47 ng/L and ND to 260.49 ng/L for OFL and NOR, respectively, and from 8.30 to 120.40 μg/L, 1.52 to 113.41 μg/L and 0.03 to 0.04 μg/L for copper (Cu), zinc (Zn) and cadmium (Cd), respectively. In terms of spatial distribution, the concentration of antibiotics in the urban sections, which had intensive human activities, was higher than that in the suburban sections, while the concentration of heavy metals in the suburban sections, which had intensive agricultural operations, was greater than that in the urban section. Ecological risk evaluation showed that NOR and OFL were present in the water bodies at a high-risk level, Cd was at a low pollution level, and the heavy metal Cd was the primary pollutant associated with health risks toward for adults and children, and it was mainly at a medium risk level. Additionally, both antibiotics and heavy metals posed higher health risks for children than for adults.