Blue oak tree-ring chronologies correlate highly with winter–spring precipitation totals over California, with Sacramento and San Joaquin river stream flow, and with seasonal variations in the salinity gradient in San Francisco Bay. The convergence of fresh and saline currents can influence turbidity, sediment accumulation, and biological productivity in the estuary. Three selected blue oak chronologies were used to develop a 625-year-long reconstruction of the seasonal salinity gradient, or low salinity zone (LSZ), which provides a unique perspective on the interannual-to-decadal variability of this important estuarine habitat indicator. The reconstruction was calibrated with instrumental LSZ data for the winter–spring season, and explains 73% of the variance in the February–June position of the LSZ from 1956 to 2003. Because this calibration period post-dates the sweeping changes that have occurred to land cover, channel morphology, and natural streamflow regimes in California, the reconstruction provides an idealized estimate for how the LSZ might have fluctuated under the seasonal precipitation variations of the past 625 years, given the modern geometry and bathymetry of the estuary and land cover across the drainage basin. The February–June season integrates precipitation and runoff variability during the cool season, and does not extend into the late-summer dry season when LSZ extremes can negatively affect Sacramento–San Joaquin Delta (Delta) agriculture and some aquatic organisms. However, there is such strong inter-seasonal persistence in the instrumental LSZ data that precipitation totals during the cool season can strongly pre-condition LSZ position in late summer. The 625-year-long reconstruction indicates strong interannual and decadal variability, the frequent recurrence of consecutive 2-year LSZ maxima and minima, large-scale ocean atmospheric forcing, and an interesting asymmetrical influence of warm El Niño–Southern Oscillation (ENSO) events.