Room-temperature ferroelectricity in two-dimensional materials offer a potential route for developing atomic-scale functional devices beyond Moore’s law. However, as a key for the technology implementations of ferroelectrics in electronics, the controllable generation of uniform domains remains challenging in two-dimensional ferroelectrics at current stage because domain engineering through an external electric field at 2D limit inevitably leads to large leakage current and material break-down. Here, we demonstrate a voltage-free method, the flexoelectric effect, to artificially generate large-scale stripe domains in two-dimensional ferroelectric CuInP2S6 with single domain lateral size at the scale of several hundred microns. With giant strain gradients (~106 m−1) at nanoscale, we mechanically switch the out-of-plane polarization in ultrathin CuInP2S6. The flexoelectric control of ferroelectric polarization is understood with a distorted Landau-Ginzburg-Devonshire double well model as evidenced by the shifted ferroelectric hysteresis loops and the first-principle calculations. Through substrate mechanical strain engineering, the stripe domain density is controllable. Our results not only highlight the potential of developing van der Waals ferroelectrics-based memories but also offer the opportunity to study ferroelectric domain physics in two-dimensional materials.