The U.S. Geological Survey maintains a program of water-quality studies in San Francisco Bay (CA) that began in 1969. This USGS Data Release archives and makes available all measurements from 2016-2021. Water-quality constituent measurements were collected aboard a research vessel. Sensor constituents include salinity, temperature, oxygen, and light attenuation coefficient. From these constituents, three parameters are derived: ratio of chlorophyll-a and pheopigments, oxygen percent saturation, and density as Sigma-t. Water sample constituents collected for later analysis include chlorophyll-a, suspended particulate matter, nitrate, nitrite, ammonium, silicate and phosphate. These discrete water samples were collected at near surface (2m) by a fixed depth pump or at depth using a Niskin water sampler on a depth-marked line. The sampling was conducted monthly at 37 fixed sampling locations along a 145-km transect from lower South San Francisco Bay to the lower Sacramento River. Additional sampling cruises at a subset of stations (South and Central Bay) were conducted 0-3 times a month. All stations are listed in the station location table (SFBay_TableofStationLocations.csv) and standard stations are shown on the map (sfbaymap.jpg). A prior USGS Data Release contains the 1969-2015 data https://www.sciencebase.gov/catalog/item/5841f97ee4b04fc80e518d9f. The project website contains more details about this research program and data collection https://sfbay.wr.usgs.gov/access/wqdata/. The website includes a public database where data from all program years can be accessed and downloaded https://sfbay.wr.usgs.gov/water-quality-database/ Please see the VersionHistory.txt for a detailed list of the updates from previous versions.