Abstract The use of hyperspectral reflectance in mineral exploration has been steadily increasing in recent decades. This study presents a novel approach that integrates geochemical and spectral proxies to delineate ore formation and alteration processes, which provide new spectral-based exploration parameters that can be used in real time. The precious metal-bearing, bimodal-felsic Northwest zone of the Lemarchant volcanogenic massive sulfide (VMS) deposits, Newfoundland, Canada, is used as a case study. Alteration associated with the Northwest zone includes intense and localized sulfide (pyrite, chalcopyrite, sphalerite, and galena) and barite enrichment, as well as quartz, white mica, and chlorite alteration. Zones of elevated Zn (>5,000 ppm) are associated with high chlorite carbonate pyrite index (CCPI), Ishikawa alteration index (AI), Ba/Sr, and low Na2O values and elevated SiO2 and K2O, Fe2O3, Na2O, and BaO contents, similar to global alteration signatures in VMS deposits. Mineralized areas contain phengitic white micas with 2,200-nm absorption features longer than 2,215 nm and Mg-rich chlorites with 2,250-nm absorption features shorter than 2,252 nm. Together, these data are consistent with the Northwest zone having undergone intense hydrothermal alteration during the mineralization event. A new lithology-normalized spectral alteration index (SAI) for white mica and chlorite was developed in order to map and characterize the alteration intensity surrounding the deposit. In addition, depth ratio parameters (2200D/2340D vs. 2250D/2340D) were used to characterize mineralogical changes and zonation. Together, these features document a paleofluid pathway with Mg chlorite alteration extending to at least 300 m away from the mineralization, outside the study area, within the andesitic and dacitic units. The use of hyperspectral reflectance coupled with geochemical alteration proxies permitted the identification of areas of intense alteration, the chemical affinities of the minerals, and their relationships to alteration processes (i.e., seawater alteration versus silicification), which would not be possible using geochemistry alone.