We report a simple method based upon coaxial electrospinning for the fabrication of aligned microfibers engraved with nanoscale grooves to promote neurite outgrowth and cell migration. The success of this method relies on the immiscibility between poly(epsilon-caprolactone) (PCL) and poly(vinyl pyrrolidone) (PVP) in 2,2,2-trifluoroethanol (TFE) for the generation of PVP/TFE pockets on the surface of a PCL jet. The pockets are stretched and elongated along with the jet, eventually resulting in the formation of nanoscale grooves upon the removal of PVP. The presence of nanoscale grooves greatly enhances the outgrowth of neurites from both PC12 cells and chick embryonic dorsal root ganglia (DRG) bodies, as well as the migration of Schwann cells. The enhancements can be maximized by optimizing the dimensions of the grooves for potential use in applications involving neurite extension and wound closure.