The fabrication and characterization of two-dimensional nanoconstriction arrays consisting of sub-20-nm graphene constrictions and interconnecting graphene islands are reported. The arrays are fabricated in a scalable top–down fashion using self-assembled close-packed polystyrene nanospheres as lithographic templates and characterized using electron microscopy, Raman spectroscopy, and charge transport measurements. At room temperature, the arrays behave as semiconductors with a field-effect conductance modulation of up to 450 and charge mobilities of ∼1 cm2 V−1 s−1. The effective bandgap of the arrays scales inversely with the nanoconstriction width, indicating that its magnitude is determined by quantum confinement in the constrictions. At low temperatures, the arrays act as semiconductors, with increasing ON/OFF conductance modulation up to ∼1000, and simultaneously act as 2D arrays of coupled Coulomb islands affected by single-electron charging events. The high conductance modulation of these nanopatterned graphene materials, combined with the scalability of the patterning approach is expected to impact thin film, flexible, and transparent semiconductor electronics.