In active, shallow, sub-volcanic magma conduits the extent of the dehydrogenation–oxidation reaction in amphibole phenocrysts is controlled by energetic processes that cause crystal lattice damage or conditions that increase hydrogen diffusivity in magmatic phases. Amphibole phenocrysts separated from dacitic volcanic rocks erupted from 1980 to 1986 and in 2005 at Mount St. Helens (MSH) were analyzed for δD, water content and Fe3+/Fe2+, and fragments of glassy groundmass were analyzed for δD and water content. Changes in amphibole δD values through time are evaluated within the context of carefully observed volcanic eruption behavior and published petrological and geochemical investigations. Driving forces for amphibole dehydrogenation include increase in magma oxygen fugacity, decrease in amphibole hydrogen fugacity, or both. The phenocryst amphibole (δD value c. –57‰ and 2 wt % H2O) in the white fallout pumice of the May 18, 1980 plinian eruptive phase is probably little modified during rapid magma ascent up an ∼7 km conduit. Younger volcanic rocks incorporate some shallowly degassed dacitic magma from earlier pulses, based on amphibole phenocryst populations that exhibit varying degrees of dehydrogenation. Pyroclastic rocks from explosive eruptions in June–October 1980 have elevated abundances of mottled amphibole phenocrysts (peaking in some pyroclastic rocks erupted on July 22, 1980), and extensive amphibole dehydrogenation is linked to crystal damage from vesiculation and pyroclastic fountain collapse that increased effective hydrogen diffusion in amphibole. Multiple amphibole δD populations in many 1980 pyroclastic rocks combined with their groundmass characteristics (e.g. mixed pumice textures) support models of shallow mixing prior to, or during, eruption as new, volatile-rich magma pulses blended with more oxidized, degassed magma. Amphibole dehydrogenation is quenched at the top surface of MSH dacite lava lobes, but the diversity in the δDamph populations in original fresh lava flow surfaces may occur from blending magma domains with different ascent histories in the sub-volcanic environment immediately before eruption. Multi-stage open-system magma degassing operated in each parcel of magma rising toward the surface, whereas the magma below ∼7 km was a relatively closed system, at least to the October 1986 eruption based on the large population of minimally dehydrogenated, rim-free amphibole in the lavas. Magma degassing and possibly H isotope exchange with low-δD fluids around the roof zone may have accompanied the ∼1·5 km upward migration of the 1980 magma body. The low-δDamph (c. –188 to –122‰) oxy-amphibole phenocrysts in lava spines extruded in May 2005 reflect dehydrogenation as ascending viscous magma degassed and crystallized, and fractures that admitted oxygen into the hot solidified lava spine interior facilitated additional iron oxidation.