Two-dimensional single-crystal PbS nanosheets were synthesized by deviatoric stress-driven orientation and attachment of nanoparticles (NPs). In situ small- and wide-angle synchrotron X-ray scattering measurements on the same spot of the sample under pressure coupled with transmission electron microscopy enable reconstruction of the nucleation route showing how enhanced deviatoric stress causes ordering NPs into single-crystal nanosheets with a lamellar mesostructure. At the same time that deviatoric stress drives SC(110) orientation in a face-centered-cubic supercrystal (SC), rocksalt (RS) NPs rotate and align their RS(200) and RS(220) planes within the SC(110) plane. When NPs approach each other along the compression axis, enhanced deviatoric stress drives soft ligands passivated at RS(200) and RS(220) surfaces to reorient from a group of SC(110) in-planes to the interspace of SC [110]-normal planes. While the internal NP structure starts a rocksalt-to-orthorhombic transition at 7.1 GPa, NPs become aligned on RS(220) and RS(200) and thus become attached at those faces. The transition-catalyzed surface atoms accelerate the inter-NP coalescing process and the formation of low-energy structure nanosheet. Above 11.6 GPa, the nucleated single-crystal nanosheets stack into a lamellar mesostructure that has a domain size comparable to the starting supercrystal.