Coastal and estuarine waters of the northern California Current system and southern Salish Sea host an observational network capable of characterizing biogeochemical dynamics related to ocean acidification, hypoxia, and marine heatwaves. Here, we compiled data sets from a set of cruises conducted in estuarine waters of Puget Sound (southern Salish Sea) and its boundary waters (Strait of Juan de Fuca and Washington coast). This data product provides data from a decade of cruises with consistent formatting, extended data quality control, and multiple units for parameters such as oxygen with different end use needs and conventions. All cruises obtained high-quality temperature, salinity, inorganic carbon, nutrient, and oxygen observations to provide insight into the dynamic distribution of physical and biogeochemical conditions in this large urban estuary complex on the west coast of North America. At all sampling stations, conductivity–temperature–depth (CTD) casts included sensors for measuring temperature, conductivity, pressure, and oxygen concentrations. Laboratory analyses of discrete water samples collected at all stations throughout the water column in Niskin bottles provided measurements of dissolved inorganic carbon (DIC), dissolved oxygen, nutrient (nitrate, nitrite, ammonium, phosphate, and silicate), and total alkalinity (TA) content. This data product includes observations from 35 research cruises, including 715 oceanographic profiles, with >7490 sensor measurements of temperature, salinity, and oxygen; ≥6070 measurements of discrete oxygen and nutrient samples; and ≥4462 measurements of inorganic carbon variables (i.e., DIC and TA). The observations comprising this cruise compilation collectively characterize the spatial and temporal variability in a region with large dynamic ranges of the physical (temperature = 6.0–21.8 ∘C, salinity = 15.6–34.0) and biogeochemical (oxygen = 12–481 µmol kg−1, dissolved inorganic carbon = 1074–2362 µmol kg−1, total alkalinity = 1274–2296 µmol kg−1) parameters central to understanding ocean acidification and hypoxia in this productive estuary system with numerous interacting human impacts on its ecosystems. All observations conform to the climate-quality observing guidelines of the Global Ocean Acidification Observing Network, the US National Oceanic and Atmospheric Administration’s Ocean Acidification Program, and ocean carbon community best practices. This ongoing cruise time series supports the estuarine and coastal monitoring and research objectives of the Washington Ocean Acidification Center and US National Oceanic and Atmospheric Administration (NOAA) Ocean and Atmospheric Research programs, and it provides diverse end users with the information needed to frame biological impacts research, validate numerical models, inform state and tribal water quality and fisheries management, and support decision-makers. All 2008–2018 cruise time-series measurements used in this publication are available at https://doi.org/10.25921/zgk5-ep63 (Alin et al., 2022).