These data were compiled as part of a long-term (1964 - 2022) water quality monitoring program at Lake Powell. Objectives of our study were to release a consistent record of long-term water quality data. The 58-year limnology dataset captures some water quality parameters (temperature, salinity, major ions, total suspended solids) from reservoir filling to present day. It also contains a 38-year record of secchi depth, and a ~30-year record of nutrients, phytoplankton, and zooplankton assemblages. The data were collected from various sites within the Lake Powell reservoir and the Glen Canyon dam. Regular monthly sampling occurred at three sites near the dam and reservoir-wide sampling was generally conducted quarterly, or least annually, at anywhere from 8 to 37 sites. Secchi depth data is taken by field observation, profile information is taken on site with a sonde or CTD, and chemistry (major ion and nutrients), phytoplankton and zooplankton data are collected via preserved water sample, that is sent to laboratories for analysis. More detailed descriptions of the monitoring program and sampling methodology can be found in two prior U.S. Geological Survey data series reports (Vernieu 2015). These data span the introduction of an invasive bivalve (Dreissena bugensis). The dataset can be used to explore long-term trends in water quality at Lake Powell reservoir as well as to inform regional, continental, and global limnology studies.