Several regions in the High Arctic still lingered poorly explored for a variety of mineralization types because of harsh climate environments and remoteness. Inglefield Land is an ice-free region in northwest Greenland that contains copper-gold mineralization associated with hydrothermal alteration mineral assemblages. In this study, Landsat-8, Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), and WorldView-3 multispectral remote sensing data were used for hydrothermal alteration mapping and mineral prospecting in the Inglefield Land at regional, local, and district scales. Directed principal components analysis (DPCA) technique was applied to map iron oxide/hydroxide, Al/Fe-OH, Mg-Fe-OH minerals, silicification (Si-OH), and SiO2 mineral groups using specialized band ratios of the multispectral datasets. For extracting reference spectra directly from the Landsat-8, ASTER, and WorldView-3 (WV-3) images to generate fraction images of end-member minerals, the automated spectral hourglass (ASH) approach was implemented. Linear spectral unmixing (LSU) algorithm was thereafter used to produce a mineral map of fractional images. Furthermore, adaptive coherence estimator (ACE) algorithm was applied to visible and near-infrared and shortwave infrared (VINR + SWIR) bands of ASTER using laboratory reflectance spectra extracted from the USGS spectral library for verifying the presence of mineral spectral signatures. Results indicate that the boundaries between the Franklinian sedimentary successions and the Etah metamorphic and meta-igneous complex, the orthogneiss in the northeastern part of the Cu-Au mineralization belt adjacent to Dallas Bugt, and the southern part of the Cu-Au mineralization belt nearby Marshall Bugt show high content of iron oxides/hydroxides and Si-OH/SiO2 mineral groups, which warrant high potential for Cu-Au prospecting. A high spatial distribution of hematite/jarosite, chalcedony/opal, and chlorite/epidote/biotite were identified with the documented Cu-Au occurrences in central and southwestern sectors of the Cu-Au mineralization belt. The calculation of confusion matrix and Kappa Coefficient proved appropriate overall accuracy and good rate of agreement for alteration mineral mapping. This investigation accomplished the application of multispectral/multi-sensor satellite imagery as a valuable and economical tool for reconnaissance stages of systematic mineral exploration projects in remote and inaccessible metallogenic provinces around the world, particularly in the High Arctic regions.