Mixed matrix membranes (MMMs), composed of functional fillers and a polymer matrix, are considered effective demonstrations for overcoming the trade-off limitation of polymeric membrane-based gas separations. MOF-74, with its high density of open metal sites and one-dimensional straight honeycomb channels, is an extremely attractive filler material. However, the intrinsically large pore aperture and micron-sized, spindle-shaped grain morphology hinder the use of high-performance, interfacial defect-free MMMs for small gas separations. Herein, we report novel mixed matrix membranes integrated with dual-metallic MOF-74 nanosheets and poly(vinylamine) for precise molecular sieving for H2 purification applications. The nanosheets of parallel orientation within the membrane maximize the exposure of channels for polymeric chain penetration. The amino side groups anchored on the polymeric chains coordinate with the open metal sites on the channel walls of MOF-74 nanosheets, exposing the hydrophobic alkyl backbones to shrink the originally large channel apertures and simultaneously enhancing the interfacial compatibility between MOF-74 and the polymer matrix. Benefiting from the merits of these elegant channel regulations, MMMs exhibit superior H2/CH4 and H2/CO2 separation performances toward binary, ternary and even quaternary feedstocks, along with remarkable long-term separation stability. This MMM is expected to constitute a new membrane paradigm that holds great promise for practical H2 purification and separation.