Lake Baiyangdian, a prominent shallow lake in the North China Plain, has historically been surrounded by numerous pharmaceutical factories and aquaculture facilities, leading to widespread antibiotic contamination. Although the implementation of pollution control measures in recent years has resulted in notable improvements in water quality, limited research has been conducted on the spatial distribution of long-term accumulated antibiotics and their potential ecological risks. To better understand the historical impacts, ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was utilized to investigate the occurrence characteristic of antibiotics in the aquatic environment, G1 evaluation method was employed to establish an antibiotic pollution assessment system and calculate the antibiotic pollution index, ecological risk entropy method was applied to evaluate the potential environmental risks of the typical antibiotics. This study focuses on the distribution patterns of 13 antibiotics, representing three classes—quinolones, sulfonamides, and macrolides—across four typical functional zones of Lake Baiyangdian, following the prohibition of aquaculture activities. The results revealed that the total antibiotic concentration in the overlying water of Lake Baiyangdian ranged from 15.52 to 256.72 ng/L, while the antibiotic concentration in the sediment ranged from 0.63 to 58.56 ng/g. Macrolides and quinolones were identified as the dominant types of antibiotic pollutants. Spatially, the total antibiotic concentration in overlying water was significantly higher in the Fuhe River inflow region compared to other regions, the dominant antibiotics in the surface water were ciprofloxacin, enrofloxacin, roxithromycin, and sulfamethazine, while the dominant antibiotics in the sediment were ofloxacin. The antibiotic pollution assessment system was found to be accurate. An in-depth study was conducted on the distribution of antibiotics across different functional zones. The results showed that antibiotic contamination in Lake Baiyangdian significantly improved after the cessation of aquaculture. The risk assessment indicated that ciprofloxacin, enrofloxacin, and ofloxacin represent a relatively high ecological risk to the Lake Baiyangdian ecosystem. This study provides scientific evidence for restoring and managing the ecosystem functions in the Lake Baiyangdian.