Microspheres with high sphericity exhibit unique functionalities. In particular, their high symmetry makes them excellent omnidirectional optical resonators. As such perfect micrometre-sized spheres are known to be formed by surface tension, melt cooling is a popular method for fabricating microspheres. However, it is extremely difficult to produce crystalline microspheres using this method because their surfaces are normally faceted. Only microspheres of polymers, glass, or ceramics have been available, while single-crystalline microspheres, which should be useful in optical applications, have been awaiting successful production. Here we report the fabrication of single-crystalline semiconductor microspheres that have surfaces with atomic-level smoothness. These microspheres were formed by performing laser ablation in superfluid helium to create and moderately cool a melt of the anisotropic semiconductor material. This novel method provides cooling conditions that are exceptionally suited for the fabrication of single-crystalline microspheres. This finding opens a pathway for studying the hidden mechanism of anisotropy-free crystal growth and its applications.