In recent years, lead-free piezoelectric nanogenerators have attracted much attention because of their great potential for harvesting energy from the environment. Here, we report the first synthesis of two-dimensional (2D) single-crystal ZnSnO hexagon nanoplates and the fabrication of ZnSnO nanoplate-based nanogenerators. The orthorhombic perovskite-structured ZnSnO nanoplates with (111) facets of the exposed plate surface are successfully synthesized via a one-step hydrothermal reaction. Piezoelectric nanogenerators are then fabricated using the as-synthesized single-crystal ZnSnO nanoplates and poly(dimethylsiloxane) (PDMS). A d value as high as 49 pC/N for the ZnSnO@PDMS composite was obtained without any electrical poling process, which demonstrates that the single-crystal ZnSnO nanoplates have a single-domain structure. To the best of our knowledge, this d value is also the highest among lead-free piezoelectric composites. A bending strain can induce the piezoelectric nanogenerator (PENG) to generate a large, stable, and sustainable output open circuit voltage of 20 V and a short circuit current of 0.6 μA, which are higher than many other PENGs. The output signals are sufficient to light a single light-emitting diode (LED), which shows the great potential of the material for scavenging mechanical energy from moving entities, such as road vehicles, railway vehicles, and humans.