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Drone-based multispectral sensing is a valuable tool for dryland spatial ecology, yet there has been limited investigation of the reproducibility of measurements from drone-mounted multispectral camera array systems or the intercomparison between drone-derived measurements, field spectroscopy, and satellite data. Using radiometrically calibrated data from two multispectral drone sensors (MicaSense RedEdge (MRE) and Parrot Sequoia (PS)) co-located with a transect of hyperspectral measurements (tramway) in the Chihuahuan desert (New Mexico, USA), we found a high degree of correspondence within individual drone data sets, but that reflectance measurements and vegetation indices varied between field, drone, and satellite sensors. In comparison to field spectra, MRE had a negative bias, while PS had a positive bias. In comparison to Sentinel-2, PS showed the best agreement, while MRE had a negative bias for all bands. A variogram analysis of NDVI showed that ecological pattern information was lost at grains coarser than 1.8 m, indicating that drone-based multispectral sensors provide information at an appropriate spatial grain to capture the heterogeneity and spectral variability of this dryland ecosystem in a dry season state. Investigators using similar workflows should understand the need to account for biases between sensors. Modelling spatial and spectral upscaling between drone and satellite data remains an important research priority.