This study provides a general procedure to generate a direct expansion (DX) cooling coil system for a roof top unit (RTU), which is a typical heating ventilation and air-conditioning (HVAC) system for commercial buildings in the United States. Experimental data from a full-scale unoccupied 2-story commercial building is used for the HVAC modeling. The regression for identifying the model coefficients was carried out with multiple stages, and the results were validated with measured data. The model’s applicability was evaluated with multiple case studies, including a building energy simulation (BES) program validation, model-based predictive control (MPC), and fault diagnostics and detection (FDD).