In order to appropriately improve the performance of sweet potato starch and expand its industrial application, sweet potato starch was modified by high pressure microfluidization (HPM) technology in this paper. The influence of HPM on sweet potato starch was studied by SEM, PLM, XRD, FTIR, DSC and rheology. The results showed that the mechanical forces generated by HPM could penetrate into the starch granules, resulting in constant changes in structure and properties of the starch granules. At 80 MPa, recrystallization phenomenon occurred inside starch granules, and the structure became more compact. 120–160 Mpa of HPM caused the breakage of the particles and the disordered arrangement of starch molecules, the relative crystallinity reduced to 25.46%, ΔH reduced to a minimum of 7.107 J/g, and the rheological behavior of starch gel changed significantly. It could be seen that HPM had significant mechanochemical effects on the sweet potato starch granules.