Molybdenum disulfide (MoS2) is a promising nonprecious catalyst for the hydrogen evolution reaction (HER) that has been extensively studied due to its excellent performance, but the lack of understanding of the factors that impact its catalytic activity hinders further design and enhancement of MoS2-based electrocatalysts. Here, by using novel porous (holey) metallic 1T phase MoS2 nanosheets synthesized by a liquid-ammonia-assisted lithiation route, we systematically investigated the contributions of crystal structure (phase), edges, and sulfur vacancies (S-vacancies) to the catalytic activity toward HER from five representative MoS2 nanosheet samples, including 2H and IT phase, porous 2H and IT phase, and sulfur-compensated porous 2H phase. Superior HER catalytic activity was achieved in the porous IT phase MoS2 nanosheets that have even more edges and S-vacancies than conventional 1T phase MoS2. A comparative study revealed that the phase serves as the key role in determining the HER performance, as IT phase MoS2 always outperforms the corresponding 2H phase MoS2 samples, and that both edges and S-vacancies also contribute significantly to the catalytic activity in porous MoS2 samples. Then, using combined defect characterization techniques of electron spin resonance spectroscopy and positron annihilation lifetime spectroscopy to quantify the S-vacancies, the contributions of each factor were individually elucidated. This study presents new insights and opens up new avenues for designing electrocatalysts based on MoS2 or other layered materials with enhanced HER performance.