In the present investigation, a commercial-purity titanium sheet was formed by a flexible sheet metal forming method, incremental sheet forming (ISF), to investigate its microstructure evolution. The deformation microstructures across the wall of formed parts were systematically examined by optical microscopy (OM), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM) and high resolution TEM (HRTEM). Microstructural evolution from millimeter- to nano-scale was explored, with special attention paid to the refinement below 100 nm. A general pattern of structural evolution begins with the formation of uni- and multi-directional twins, which is accompanied by the initiation and development of ultrafine lamellar structure and final evolution of nano-lamellar structure and nano-equiaxed structure. A twinning-dominated process that was supplemented with dislocation slip-dominated one governed the microstructural evolution toward nano-regime. The strain-induced evolution of nano-lamellar and nano-equiaxed structures were discussed, of which the underlying refinement mechanism was analyzed. This technique was promising to offer an optional route for realizing the strengthening of metal parts via synthesizing nanostructures, showing potential scientific and technological importance in fabricating the high-strength metal formed productions for further meeting industrial applications.