Over a two-year period (2010–2011), in-place measurements were made and water-quality samples were collected from 122 lakes in the Yukon Flats, Alaska, during a U.S. Geological Survey lake biological diversity inventory. The U.S. Geological Survey National Research Program performed the chemical analyses on the retrieved water-quality samples. Results from the analyses of water samples for dissolved carbon gases and carbon isotopes, hydrogen and oxygen stable isotopes, dissolved organic carbon, and major cations and anions, along with supporting site data, are presented in this report.