In this work, we present an exfoliation method that produces cm²-area atomically flat surfaces from bulk layered single crystals, with broad applications such as for the formation of lateral heterostructures and for use as substrates for van der Waals epitaxy. Single crystals of Bi₂Se₃ were grown using the Bridgman method and examined with X-ray reciprocal space maps, Auger spectroscopy, low-energy electron diffraction, and X-ray photoelectron spectroscopy. An indium-bonding exfoliation technique was developed that produces multiple ∼100 μm thick atomically flat, macroscopic (>1 cm²) slabs from each Bi₂Se₃ source crystal. Two-dimensional X-ray diffraction and reciprocal space maps confirm the high crystalline quality of the exfoliated surfaces. Atomic force microscopy reveals that the exfoliated surfaces have an average root-mean-square (RMS) roughness of ∼0.04 nm across 400 μm² scans and an average terrace width of 70 μm between step edges. First-principles calculations reveal exfoliation energies of Bi₂Se₃ and a number of other layered compounds, which demonstrate relevance of our method across the field of 2D materials. While many potential applications exist, excellent lattice matching with the III–V alloy space suggests immediate potential for the use of these exfoliated layered materials as epitaxial substrates for photovoltaic development.