Water temperature is an important factor determining estuarine species habitat conditions. Water temperature is mainly governed by advection (e.g., from rivers) and atmospheric exchange processes varying strongly over time (day-night, seasonally) and the spatial domain. On a long time scale, climate change will impact water temperature in estuarine systems due to changes in river flow regimes, air temperature, and sea level rise. To determine which factors govern estuarine water temperature and its sensitivity to changes in its forcing, we developed a process-based numerical model (Delft3D Flexible Mesh) and applied it to a well-monitored estuarine system (the San Francisco Estuary) for validation. The process-based approach allows for detailed process description and a physics-based analysis of governing processes. The model was calibrated for water year 2011 and incorporated 3-D hydrodynamics, salinity intrusion, water temperature dynamics, and atmospheric coupling. Results show significant skill in reproducing temperature observations on daily, seasonal, and yearly time scales. In North San Francisco Bay, thermal stratification is present, enhanced by salinity stratification. The temperature of the upstream, fresh water Delta area is captured well in 2-D mode, although locally—on a small scale—vertical processes (e.g., stratification) may be important. The impact of upstream river temperature and discharge and atmospheric forcing on water temperatures differs throughout the Delta, possibly depending on dispersion and residence times. Our modeling effort provides a sound basis for future modeling studies including climate change impact on water temperature and associated ecological modeling, e.g., clam and fish habitat and phytoplankton dynamics.