Recently, the formation of superabundant vacancies has always been found to accompany hydrogen charging. As an elemental point defect, vacancies can cause bond loss, be absorbed by dislocations, or cluster to form void embryos etc. In hydrogenated metal, a vacancy usually absorbs multiple hydrogen to become a hydrogenated vacancy (VaHn), which behave differently from naked vacancies. Although the high concentration of VaHn can be closely related to hydrogen damage/embrittlement, this argument is still poorly supported by direct experimental evidence, especially at the microstructural/defect level. Inside an environmental transmission electron microscope (ETEM), we systematically studied the hydrogen-microstructure interaction using high resolution observation and well-controlled mechanical testing on single-crystal aluminum samples, in vacuum and in pure hydrogen environment respectively. The results of cyclic compression tests on sub-micron pillars show that after hydrogenation, the Young’s modulus of aluminum decreases by about 3%. Moreover, dislocation motions can be locked/unlocked by hydrogenation/degassing, a scenario at odds with previous experimental observations. In situ observations show that hydrogen charging can facilitate dislocation climb, as well as the formation of nanocavities, which can evolve towards giant cavities if heated up to ~200 °C. The mechanisms behind these observed hydrogen-induced phenomena can be well explained by taking VaHn into consideration, implying a broad impact by the elevated concentration of VaHn across multiple size levels from atomic bonds to dislocation behavior and interface cohesion. Our in-situ observations and quantitative mechanical measurements in aluminum offer key information for revealing the underlying mechanism of hydrogen embrittlement/damage.