Rational design and precise fabrication of catalysts with high active site exposure and efficient charge transport are highly desirable but challenging. Herein, we report a unique strategy to construct well-defined and mixed-dimensional W17O47-MoS2 heterostructures, where ultrathin MoS2 nanolayers vertically rooted onto W17O47 nanowires in edge-contact geometry. The in situ etching approach simultaneously created high accessible anion-deficit sites for refined electronic structures and intimate heterointerface for spatial charge-flow-steering. The best W17O47-MoS2, with optimized MoS2 loading, exhibited a MoS2 mass activity 116-fold higher than that of pure MoS2 in electrocatalytic hydrogen evolution reaction. Density functional theory calculations unveiled that low-coordination sites and intimate interfaces induced the synergy of interface-O and edge-Mo atoms, substantially regulating the electron distribution of active sites in the critical hydrogen activation step. This work not only provided a platform for understanding the origin of catalytic activity, but also brought instructive design criteria for constructing heterostructures in catalysis, photonics, and electronics.