This U.S. Geological Survey (USGS) data release presents water-quality and bathymetric data measured with an Autonomous Underwater Vehicle (AUV) during spatial surveys in the Cape Fear River near Lock and Dam 1 near Riegelwood, NC in 2020 and at the confluence of the Haw and Deep Rivers near Moncure, NC in 2021. The Cape Fear River Basin is contained entirely within North Carolina and has a drainage area of 3,464 square miles. Four data collection trips were conducted that included 21 surveys. Data from each survey are presented in a CSV file, named with the survey date, time, and location. Data were measured by the AUV and logged at 0.25-second intervals. The AUV was equipped with a YSI EXO1 multiparameter sonde with sensors to measure the following water-quality parameters: water temperature (degrees Celsius; YSI Sensor 599870), specific conductivity (microSiemens per centimeter at 25 degrees Celsius; YSI sensor 599870), phycocyanin fluorescence (relative fluorescence units; YSI sensor 599102-01), chlorophyll fluorescence (relative fluorescence units; YSI sensor 599103-01), dissolved oxygen (milligrams per liter; YSI sensor, 599100-01), and turbidity (formazin nephelometric units; YSI sensor 599101-01) (YSI, 2019). Sensors were calibrated before and checked after, each data collection trip per USGS water-quality sampling protocols. See Data Quality section for additional information related to calibration and checks. Bathymetric data were measured with an on-board depth sounder and pressure transducer. Parameters include depth from surface, depth to bottom, and total water column. See Data Quality section for additional information related to positional accuracy and corrections.