The primary objective of the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS‐REx) mission is to return to Earth a pristine sample of carbonaceous material from the primitive asteroid (101955) Bennu. To support compositional mapping of Bennu as part of sample site selection and characterization, we tested 95 spectral indices on visible to near infrared laboratory reflectance data from minerals and carbonaceous meteorites. Our aim was to determine which indices reliably identify spectral features of interest. Most spectral indices had high positive detection rates when applied to spectra of pure, single‐component materials. The meteorite spectra have fewer and weaker absorption features and, as a result, fewer detections with the spectral indices. Indices targeting absorptions at 0.7 and 2.7–3 μm, which are attributable to hydrated minerals, were most successful for the meteorites. Based on these results, we identified a set of 17 indices that are most likely to be useful at Bennu. These indices detect olivines, pyroxenes, carbonates, water/OH‐bearing minerals, serpentines, ferric minerals, and organics. Particle size and albedo are known to affect band depth but had a negligible impact on interpretive success with spectral indices. Preliminary analysis of the disk‐integrated Bennu spectrum with these indices is consistent with expectations given the observed absorption near 3 μm. Our study prioritizes spectral indices to be used for OSIRIS‐REx spectral analysis and mapping and informs the reliability of all index‐derived data products, including a science value map for sample site selection.