Natural ventilation has been used to increase indoor air quality, remove pollutants, and remove heat absorbed in the building structure. Some architectural features such as wind-catcher systems are used to induce airflow into buildings, and openings equipped with louvers are employed to reduce solar daylight while allowing natural ventilation. Earlier studies on ventilated louvers and wind-catchers have shown the impact of the louvers’ opening positions and slat angles. However, their combination with each other has been less studied. This paper presents CFD simulations of cross-ventilation in a generic isolated building integrated with a one-sided roof-top wind-catcher and the outlet opening, both equipped with louvers for three different window opening positions. The isothermal 3D steady RANS equations were solved with the Standard k- ε method. The CFD simulations with CFX software were validated with the wind-tunnel experiments. The results show that the lowest dimensionless wind velocities inside the building were observed for the arrangement “Down” for both cases with and without louvers. In contrast, the highest air exchange efficiency and dimensionless wind velocities inside the building were measured for the arrangement “Up” for the case with louvers. This research can be considered as an architectural strategy to improve indoor natural cross-ventilation.