This data release includes multispectral images and field measurements of water depth from the Sacramento River near Glenn, California, used to evaluate the potential for efficient reach-scale mapping of river bathymetry using Uncrewed Aircraft Systems (UAS). The images were acquired by a MicaSense RedEdge-MX Dual Camera deployed from a Trinity F90 vertical take-off and landing (VTOL) UAS. The 4 km long study area along the Sacramento River was subdivided into three distinct but adjacent areas of interest (AOIs) and image data were collected from one AOI each day between September 14 and 16, 2021. The image data were ortho-rectified using Quantum-Systems QBase 3D and Agisoft Metashape software and saved as GeoTIFF files. A header text file is also included with each of the images and includes information on the 10 bands of the MicaSense RedEdge-MX Dual Camera, which include: Band 1 (Coastal blue): 444 nm Band 2 (Blue): 475 nm Band 3 (Green): 531 nm Band 4 (Green): 560 nm Band 5 (Red): 650 nm Band 6 (Red): 668 nm Band 7 (Red Edge): 705 nm Band 8 (Red Edge): 717 nm Band 9 (Red Edge): 740 nm Band 10 (Near Infrared): 842 nm Each image has an associated ENVI format header text file that also contains this spectral information. The pixel values for these images are digital numbers between 0 and 65535 for all 10 spectral bands. To convert these digital numbers to reflectance values between 0 and 1, divide each pixel value in each band by 32768. To display the images as a familiar true-color composite, band 5 can be displayed as red, band 4 as green, and band 2 as blue. Water depths were measured directly in the field to calibrate relationships between depth and reflectance and to assess the accuracy of image-derived depth estimates. In shallow areas along the margins of the channel, depth measurements were made while wading with a Trimble R10 real-time kinematic (RTK) global navigation satellite system (GNSS) receiver to record spatial coordinates and riverbed elevations. Additional points along the edge of the water were surveyed to capture the water surface elevation and depths for points within the channel were calculated by subtracting the local bed elevation from the nearest water surface elevation. For deeper areas that could not be waded safely, another Trimble R10 RTK GNSS receiver was mounted on a boat with an outboard motor and connected to a Seafloor Systems SonarMite echo sounder that measured the water depth. The boat-based data were collected along a series of 25 channel-spanning cross sections and one longitudinal profile that extended over the full length of the study area. The map projection and datum for the shapefiles and GeoTIFF images contained in this data release are UTM Zone 10 N and NAD83, respectively. Each shapefile has coordinates in units of meters and the depth measurements are also in meters.