Texas A and M University has been operating a large-scale, UAV-based, agricultural remote-sensing research project since 2015. To use UAV-based images in agricultural production, many high-resolution images must be mosaicked together to create an image of an agricultural field. Two key difficulties to science-based utilization of such mosaics are geographic registration and radiometric calibration. In our current research project, image files are taken to the computer laboratory after the flight, and semi-manual pre-processing is implemented on the raw image data, including ortho-mosaicking and radiometric calibration. Ground control points (GCPs) are critical for high-quality geographic registration of images during mosaicking. Applications requiring accurate reflectance data also require radiometric-calibration references so that reflectance values of image objects can be calculated. We have developed a method for automated geographic registration and radiometric correction with targets that are installed semi-permanently at distributed locations around fields. The targets are a combination of black (≈5% reflectance), dark gray (≈20% reflectance), and light gray (≈40% reflectance) sections that provide for a transformation of pixel-value to reflectance in the dynamic range of crop fields. The exact spectral reflectance of each target is known, having been measured with a spectrophotometer. At the time of installation, each target is measured for position with a real-time kinematic GPS receiver to give its precise latitude and longitude. Automated location of the reference targets in the images is required for precise, automated, geographic registration; and automated calculation of the digital-number to reflectance transformation is required for automated radiometric calibration. To validate the system for radiometric calibration, a calibrated UAV-based image mosaic of a field was compared to a calibrated single image from a manned aircraft. Reflectance values in selected zones of each image were strongly linearly related, and the average error of UAV-mosaic reflectances was 3.4% in the red band, 1.9% in the green band, and 1.5% in the blue band. Based on these results, the proposed physical system and automated software for calibrating UAV mosaics show excellent promise.