Environmental time series have rich information content that is invaluable for measuring and understanding changes over time and guiding policies to manage change. I extracted information from measurements of 10 water‐quality constituents in upper San Francisco Bay from 1975 to 2016, one of the longest observational records in a U.S. estuary. Changes were detected at every time scale captured by monthly sampling. Long‐term trends included increased ammonium (+53%), nitrate + nitrate (+50%), silicate (+14%), Secchi depth (+42%), and decreased chlorophyll a (Chl a) (−74%) and suspended particulate matter (−45%). Changes at the decadal scale included abrupt shifts (Chl a, nitrate + nitrite) and oscillations between shorter trends of increase and decrease (Secchi depth, phosphate). Long‐term trends were not expressed equally across all seasons, and seasonal patterns of change varied across constituents. These examples illustrate key features of environmental variability at the land–sea interface: (1) water‐quality components change continually at time scales from months to decades; (2) patterns of seasonal, multiyear, and multidecadal change are complex and vary across constituents; (3) primary drivers of change are freshwater inflow, the master regulator of estuarine dynamics, and human activities such as river damming, water diversions, wastewater discharge, environmental policies, and species introductions; (4) extracting the full information content of time series requires multiple analyses, each revealing a different layer of insight into how changes develop over time; (5) water‐quality variability is nonstationary, so future changes cannot be forecast reliably; (6) repeated observation is an essential method of Earth system science with applications in the design and performance measures of environmental policies.