As a result of the widespread use of antibiotics, a large amount of excretions from human and animals, containing antibiotic residues, is discharged into aquatic environments, leading to potential adverse effects on the ecosystems' health. These residues' impact on seasonally ice-covered rivers remains under investigated. To understand the environmental fate of antibiotics with high-detection frequencies and concentration levels, sulfamethoxazole, lincomycin, and florfenicolwere used asmodels in the present study. A Level IV fugacity model was established and applied to a seasonally ice-covered river receiving municipal wastewater treatment plant (WWTP) effluents, the Songhua River in Northeast China. Model validation and sensitivity analysis suggested that the fugacity model could successfully simulate the monitoring concentration within an average difference of one logarithmic unit. The advection process played a major role in the transport and attenuation of the antibiotics in the ice-covered river receiving WWTP effluents. The scenario simulation indicated that increasing the targeted antibiotic concentrations in WWTP effluents to μg L−1 could keep the targeted antibiotic concentrations higher than 10 ng L−1 in the receiving river from the WWTP discharge source to 25 km downstream. This finding also demonstrates that the depth of water and ice, as well as flow velocity, play key roles in the fate of antibiotics in the ice-covered river receiving WWTP effluents. To our best knowledge, this is the first major study to combine experimental investigation with modeling to explore the environmental behaviors and fate of antibiotics in such a river.