The main objective of this study was to develop and test a framework that can be used by Unmanned Aerial Systems (UAS) operators with varying technical backgrounds to estimate the accuracy and reliability of multispectral (visible and Near-Infrared or NIR) sensor measurements. We evaluated the performance of two multispectral sensors – the MicaSense RedEdge and the Airinov MultiSpec 4C – in both a laboratory and field setting. In the laboratory, we measured the reflectance of a number of reference target materials using each UAS sensor, and compared the values to those measured using a calibrated spectrometer. We found a strong linear relationship between the measurements made by the MicaSense RedEdge and the spectrometer, while the relationship was much weaker for the Airinov MultiSpec 4C, particularly in the longer wavelength bands (red-edge and NIR). A sub-set of the target materials were selected as ground reference targets for three field calibration exercises. In field calibration assessment No. 1, imagery was collected using each UAS sensor and reflectance values were extracted from pixels covering the ground reference targets. The extracted values were compared to the reflectance values acquired in the laboratory, and both UAS sensors were found to over-estimate reflectance, with lower accuracy in red-edge and NIR bands. Field calibration assessment No. 2 involved a calculation of Normalized Difference Vegetation Index (NDVI) values at field control points using both UAS sensors, and we found a strong linear relationship between the NDVI values and measurements made by a hand-held NDVI sensor, suggesting that the calculation of a normalized band ratio (i.e., NDVI) effectively reduces the reflectance measurement inaccuracy that we observed previously. Field calibration assessment No. 3 included image acquisition of ground reference targets using the MicaSense RedEdge sensor over seventeen sequential field surveys. Results revealed measurement variability over time, suggesting that daily differences in solar illumination and atmospheric conditions may influence derived reflectance values. In light of these results, we propose simplified procedures that can be adopted by UAS operators to periodically assess the radiometric fidelity of their multispectral sensors.