Microplastics (MPs), as carriers of organic pollutants in the environment, have become a growing public concern in recent years. Tetracycline (TTC) is an antibiotic that can be absorbed by MPs and have a harmful effect on human health. Therefore, this study was conducted with the aim of investigating the adsorption rate of TTC onto polyvinyl chloride (PVC) MPs. In addition, the adsorption mechanism of this process was studied using isothermal, kinetic, and thermodynamic models. For this purpose, experimental runs using the Box-Behnken model were designed to investigate the main research parameters, including PVC dose (0.5–2 g/L), reaction time (5–55 min), initial antibiotic concentration (5–15 mg/L), and pH (4–10). Based on the research findings, the highest TTC adsorption rate (93.23%) was obtained at a pH of 10, a contact time of 55 min, an adsorbent dose of 1.25 g/L, and an antibiotic concentration of 10 mg/L. The study found that the adsorption rate of TTC followed the pseudo-second-order and Langmuir models. Thermodynamic data indicated that the process was spontaneous, exothermic, and physical. Increasing ion concentration decreased TTC adsorption, and distilled water had the highest adsorption, while municipal wastewater had the lowest adsorption. These findings provide valuable insights into the behavior of MPs and organic pollutants, underscoring the importance of conducting additional research and implementing measures to mitigate their detrimental effects on human health and the environment.