Microplastics (MPs) carry and spread environmental pollutants far and wide. The surface structure of MPs changes when MPs are exposed to light, and which influences the adhesion of MPs to pollutants. In this study, ultraviolet (UV) irradiation (1000 W mercury lamp, 80W/cm2) was utilized to simulate the aging of PVC MPs in natural environments. The adsorption and desorption behaviors of PVC MPs on tildipirosin were investigated. Furthermore, Escherichia coli was used for antibiotic stress experiments. The results revealed that aged PVC MPs exhibited a new oxygen-containing absorption peak at 1736 cm−1, attributing to the stretching of a C = O. Notably, tildipirosin adsorption by the pristine PVC MPs conformed to the pseudo-first-order kinetic model (R2 = 0.975), while the aged PVC MPs followed the pseudo-second-order kinetic model. The adsorption process followed the Langmuir thermodynamic equation. Furthermore, the desorption rates of the pristine, 6-day-aged, and 12-day-aged PVC MPs were determined to be 24.2%, 24.3%, and 30.7%, respectively. Thus, the data indicated that tildipirosin was more easily desorbed from the aged PVC MPs. pH studies showed that electrostatic forces significantly impacted tildipirosin adsorption. The antibiotics stress experiments demonstrated that Escherichia coli K12 could tolerate a higher concentration (40 mg/L) of tildipirosin undergoing the domestication with low concentration (12.8 mg/L tildipirosin) sequential stress. The findings of this study are expected to contribute to the understanding of the synergistic behavior of MPs and antibiotics in the environment and the ecological risks involved.