This paper systematically investigates the indoor airflow and contaminant dispersion of diffuse ceiling ventilation (DCV) for space heating and cooling. A numerical model of the office with DCV is built and validated. The indoor thermal comfort and air quality (IAQ) under different cases are analyzed. Simultaneously, different indices are employed to determine the influence of exhaust positions and air change rates on the system. The results indicate that DCV can provide a satisfying thermal environment both in heating and cooling modes, and there is no reverse flow from the room to the plenum. Besides, the visualizations of indoor airflow, temperature distributions, and mean age of air (MAA) show the different characteristics during heating and cooling. The ranges of contaminant removal effectiveness (CRE) and temperature effectiveness (TE) are 0.87–1.00 and 0.79–1.55 for heating, respectively. For cooling, they are 0.96–1.23 (CRE) and 0.92–1.06 (TE), respectively. Although the TE for heating is slightly higher than that of cooling, the CO2 concentrations and CRE manifest that DCV performs better for space cooling. Moreover, the results show that the exhaust positions influence TE more than CRE, especially for heating. Within the measured air change rates, it is found that the increase of air change per hour (ACH) can aid to the ventilation effectiveness of DCV. Meanwhile, the linear regression equations between ACHs and MAA are obtained. This research is helpful to reveal the flow mechanisms of DCV and guides the design and operation of the system.