Moiré effects in vertical stacks of two-dimensional crystals give rise to new quantum materials with rich transport and optical phenomena that originate from modulations of atomic registries within moiré supercells. Due to finite elasticity, however, the superlattices can transform from moiré-type to periodically reconstructed patterns. Here we expand the notion of such nanoscale lattice reconstruction to the mesoscopic scale of laterally extended samples and demonstrate rich consequences in optical studies of excitons in MoSe2–WSe2heterostructures with parallel and antiparallel alignments. Our results provide a unified perspective on moiré excitons in near-commensurate semiconductor heterostructures with small twist angles by identifying domains with exciton properties of distinct effective dimensionality, and establish mesoscopic reconstruction as a compelling feature of real samples and devices with inherent finite size effects and disorder. Generalized to stacks of other two-dimensional materials, this notion of mesoscale domain formation with emergent topological defects and percolation networks will instructively expand the understanding of fundamental electronic, optical and magnetic properties of van der Waals heterostructures.