The objective of this study is to investigate the mechanism of inter-flat airborne disease transmission under the condition of single-sided natural ventilation. The focus is on one of the typical designs in residential buildings with a rectangular plan layout and having a common corridor separating the two sides, each of which has a flat faade with openable windows. When the wind speed is extremely low, with doors closed and windows opened, the flats become single-sided naturally ventilated driven by buoyancy effects. The air pollutants can travel from a lower flat to a vertically adjacent upper flat through open windows, caused by indoor/outdoor temperature-difference induced buoyancy. Computational fluid dynamics is employed to explore the characteristics of this process. Based on the comparison with experimental data about the air flow distribution in and around a single-sided naturally ventilated room, the renormalization group based k-ε model, together with carbon dioxide used as a tracer, is chosen to reveal this air cross-contamination. The simulation results are in agreement with our prior on-site tracer-gas measurements, revealing that the windows flush with a flat faade can be a major route of the air cross-contamination in high-rise residential buildings. Finally, an assessment index is proposed to evaluate the potential infection risks associated with this inter-flat air flow occurring in high-rise residential buildings.