Scheelite (CaWO4) collected from 37 different ore-deposit settings (orogenic, sediment- and greenstone-hosted, skarn, porphyry, greisen, volcanogenic massive sulfide, breccia, and polymetallic deposits) globally was examined and evaluated using a combination of cathodoluminescence (CL), SEM-EDS, LA-ICP-MS, and δ18O analytical methods. These data provided the basis to assess whether the crystal-chemistry of scheelite could be used to distinguish between differing environments of formation. The results show: (1) scheelite can record very complex growth histories based on CL images and elemental mapping; (2) predominant elemental substitutions involve As5+ or Mo6+ ↔ W6+ and Sr2+ or REE3+ ↔ Ca2+; (3) highly variable trends for the REEs that vary in terms of ΣREEs (below detection to 104 range in CN values), the degree and nature of fractionation (i.e., flat, convex, concave), and the nature of EuN values, which are both positive and negative, with Eu anomalies (EuA) ranging from <0.1 to >20–30; and (4) δ18O values varying from –4.6 to +12.7‰, which apparently do not relate to a deposit-specific fluid signature (δ18OH2O). The variability in REE patterns suggests that many factors affect both ΣREE and incorporation, hence the observed fractionation, into scheelite (e.g., fluid chemistry, coprecipitation of other REE-bearing minerals). Substitutions involving Mo and As are of particular relevance, as both elements are redox sensitive and their enrichment is reflected in ore-deposit settings such that reduced orogenic-type Au-W deposits are As and Mo depleted in contrast to the more oxidized intrusion-related deposits where Mo is enriched (>100 ppm). Similarly, both the EuA values and Sr are relatively enriched in orogenic settings versus intrusion-related settings. These observed chemical differences for Sr, Mo, and EuA in scheelite from different deposit settings were used to construct the first ever discriminant diagram for scheelite, which is summarized in a plot of EuAversus Sr/Mo, which successfully discriminates the samples used in this study. Thus, the crystal-chemistry of scheelite is shown to be both a strong indicator of ore-forming conditions and an ore-deposit discriminator.