One of the bottlenecks in realizing the potential of atom-thick graphene membrane for gas sieving is the difficulty in incorporating nanopores in an otherwise impermeable graphene lattice, with an angstrom precision at a high-enough pore density. We realize this design by developing a synergistic, partially decoupled defect nucleation and pore expansion strategy using O2 plasma and O3 treatment. A high density (ca. 2.1 × 1012 cm-2) of H2-sieving pores was achieved while limiting the percentage of CH4-permeating pores to 13 to 22 parts per million. As a result, a record-high gas mixture separation performance was achieved (H2 permeance, 1340 to 6045 gas permeation units; H2/CH4 separation factor, 15.6 to 25.1; H2/C3H8 separation factor, 38.0 to 57.8). This highly scalable pore etching strategy will accelerate the development of single-layer graphene-based energy-efficient membranes.