Many emerging technologies require materials with well-defined 3D nanoscale architectures. Production of these structures is currently underpinned by self-assembling amphiphilic macromolecules or engineered all-DNA building blocks. Both these approaches produce restricted ranges of crystal geometries due to synthetic amphiphiles’ simple shape and limited specificity, or the technical difficulties in designing space-filling DNA motifs with targeted shapes. We have overcome these limitations with amphiphilic DNA-nanostructures, or “C-Stars”, that combine the design freedom and facile functionalization of DNA-based materials with robust hydrophobic interactions. C-Stars self-assemble into single crystals exceeding 40 μm in size with lattice parameters exceeding 20 nm.