This dataset includes field measurements and laboratory analyses of surface water, bottom water (sediment-water interface), surficial (0-2 cm) sediment, pore water (0-2 cm), and biota collected in Lake Combie, California, from September 2017 through August 2021. The study area includes six sites within the reservoir where discrete samples of surface water, bottom water, sediment, and pore water were taken along the length of the reservoir at the following distances from the spillway: 0.07 miles, 0.5 miles, 0.9 miles, 1.2 miles, 1.3 miles, and 1.4 miles. The within-reservoir sites were sampled during September 2017, February 2018, and May 2018, prior to a large sediment removal operation, and again during September 2019, February 2020, and June 2020 following the removal operation. Zooplankton samples were collected at four of the six sites during the sampling period. Fish were collected from within two regions of the lake: in the Wooley Creek arm of the lower reservoir, and in the upper reservoir near the targeted area for sediment removal operations. Vertical profiles of water quality were measured with a multi-parameter sonde during water collection events and during one zooplankton event. Thirty-six surface water and thirty-six bottom water samples were collected at each site and analyzed for total mercury (filtered and particulate), methylmercury (filtered and particulate), total suspended solids, sulfate, chloride, selected dissolved nutrients, particulate 13-C/12-C and 15-N/14-N isotopic ratios, total particulate carbon and nitrogen, particulate carbon to nitrogen molar ratio, dissolved organic carbon, and dissolved organic-matter properties (absorption and fluorescence). Thirty-six bed-sediment samples were analyzed for total mercury, methylmercury, total reduced sulfur, and organic content. Pore water extracted from bed sediment was analyzed for filtered total mercury, filtered methylmercury, sulfate, chloride, selected dissolved nutrients, and dissolved organic carbon. Surface water, bottom water, and sediment collections included an additional four field replicates each for analysis - pore water had six replicates. One hundred six zooplankton samples and twenty-three replicates were analyzed for total mercury, methylmercury, 13-C/12-C isotopic ratio, and 15-N/14-N isotopic ratio. Two hundred ninety fish samples were analyzed for total mercury, methylmercury, 13-C/12-C isotopic ratio, 15-N/14-N isotopic ratio, and total mass carbon and nitrogen. Water-quality field measurements made with a multi-parameter sonde included water temperature, barometric pressure, specific conductance, dissolved oxygen, pH, and turbidity. The within-reservoir data includes seven data tables given as both machine readable tab-delimited text (.txt) and Excel formats (.xlsx): 1) DataDictionary_LCR17-21, the data dictionary, which provides definitions and details related to the six other data tables, and includes citations of analytical methods; 2) SurfWater_Field-Lab_LCR17-20, the surface water and bottom water data table; 3) Sediment_LCR17-20; 4) PoreWater_LCR17-20; 5) Zooplankton_LCR17-20; 6) Fish_LCR18-21; and 7) SurfWater_Profiles_LCR17-20.