The U.S. Geological Survey and other federal and state agencies have been collecting continuous temperature and salinity data, two critical estuarine habitat variables, throughout San Francisco estuary for over two decades. Although this dynamic, highly variable system has been well studied, many questions remain relating to the effects of freshwater inflow and other physical and biological linkages. This study examines up to 20 years of publically available, continuous temperature and salinity data from 10 different San Francisco Bay stations to identify trends in temperature and salinity and quantify the salinity–freshwater inflow relationship. Several trends in the salinity and temperature records were identified, although the high degree of daily and interannual variability confounds the analysis. In addition, freshwater inflow to the estuary has a range of effects on salinity from −0.0020 to −0.0096 (m³ s⁻¹) ⁻¹ discharge, depending on location in the estuary and the timescale of analyzed data. Finally, we documented that changes in freshwater inflow to the estuary that are within the range of typical management actions can affect bay-wide salinities by 0.6–1.4. This study reinforces the idea that multidecadal records are needed to identify trends from decadal changes in water management and climate and, therefore, are extremely valuable.