Electrochemical water splitting is very attractive for green fuel energy production, but the development of active, stable, and earth-abundant catalysts for the hydrogen evolution reaction (HER) remains a major challenge. Here, core-shell nanostructured architectures are used to design and fabricate efficient and stable HER catalysts from earth-abundant components. Vertically oriented quasi-2D core-shell MoO2/MoSe2 nanosheet arrays are grown onto insulating (SiO2/Si wafer) or conductive (carbon cloth) substrates. This core-shell nanostructure array architecture exhibits synergistic properties to create superior HER performance, where high density structural defects and disorders on the shell generated by a large crystalline mismatch of MoO2 and MoSe2 act as multiple active sites for HER, and the metallic MoO2 core facilitates charge transport for proton reduction while the vertical nanosheet arrays ensure fully exposed active sites toward electrolytes. As a HER catalyst, this electrode exhibits a low Tafel slope of 49.1 mV dec(-1), a small onset potential of 63 mV, and an ultralow charge transfer resistance (R-ct) of 16.6 Omega at an overpotential of 300 mV with a long cycling durability for up to 8 h. This work suggests that a quasi 2D core-shell nanostructure combined with a vertical array microstructure is a promising strategy for efficient water splitting electrocatalysts with scale-up potential.