At low-temperature and high-stress conditions, quartz deformation is controlled by the kinetics of dislocation glide, often referred to as low-temperature plasticity (LTP). To investigate the relationship between intracrystalline H2O content and the yield strength of quartz during LTP, we have integrated spherical and Berkovich nanoindentation tests at room temperature on natural quartz grains from a deformed migmatitic gneiss with electron backscatter diffraction (EBSD) and secondary-ion mass spectrometry (SIMS) measurements of intracrystalline H2O content. Dry (<20 wt ppm H2O) and wet (20–100 wt ppm H2O) crystals exhibit comparable indentation hardness, which is proportional to quartz yield strength. Thus, quartz yield strength, seems to be unaffected by the intracrystalline H2O content. Pre-indentation strain history may have had a major role in generating a high density of dislocation sources, which controlled the yield stress during LTP.