Real-time, high frequency (1-second sample interval) GPS location, water quality, and water isotope (δ2H, δ18O) data was collected in the Cache Slough Complex (CSC), located in the northern San Francisco Bay Delta (SFBD). Data was collected on 10/01/2014 for an approximate 4-hour period (10:30 – 14:30 h PST) while underway on the R/V Mary Landsteiner, a 26-foot USGS vessel. Sample water was pumped continuously through a pickup tube, passed through a 178 micron pre-filter, a de-bubbler, and diverted through a 0.2 micron filter and an unfiltered flow path to water quality instrumentation. The real-time data were recorded using a Campbell Scientific CR-6 data logger. Water isotopes (δ2H, δ18O) were logged to a separate CSV file in real-time. Methods of collection and instrumentation configuration are outlined in Downing et al. 2016. Water quality data was processed using a Microsoft Excel (v. 15.0) macro designed to remove outliers using a 20 second median, followed by a 30 second average. Isotope data was normalized to the VSMOW-SLAP scale using methods described in Downing et al. 2016. Data was merged into one Microsoft Excel file in MATLab. The data file includes: date, time, latitude, longitude, estimated boat distance, estimated boat speed, temperature, specific conductance, pH, dissolved oxygen, turbidity, fDOM, Chlorophyll-a, Phycocyanin, transmission and attenuation (670 nm), nitrate, water isotopes (δ2H, δ18O), calculated evaporation to inflow ratio, standard deviation of evaporation to inflow ratio, calculated water residence time, and standard deviation of water residence time. These data support the following publication: Using continuous underway isotope measurements to map water residence time in hydrodynamically complex tidal environments. Downing, B.D., Brian A. Bergamaschi, Carol Kendall, Tamara E.C. Kraus, Kate J. Dennis, Jeffery A. Carter, and Travis S. von Dessonneck. Environmental Science & Technology 2016 50 (24), 13387 – 133396. DOI: 10.1021/acs.est.6b05745.