Chiral switching is a fascinating topic and plays an important role in construction of homochirality. Nevertheless, due to the complexity and flexibility of noncovalent interactions, switching the chirality of entire supramolecular assemblies has hitherto remained a challenge. Here we report the electric field-controlled chirality switching of pentacene pinwheel arrays and two-dimensional (2D) network domains. Pentacene molecules on Cd(0001) surface form the porous network structure with building blocks of hexamer pinwheels. Driven by the electric field from a scanning tunneling microscopy (STM) tip, the supramolecular chirality of pentacene pinwheels and the organizational chirality of entire network domains can be simultaneously switched from one enantiomorph to another. Furthermore, such chiral switching is reversible and repeatable under successive voltage pulses. First-principles calculations demonstrate that electric field significantly modulates the interfacial charge transfer and induces the Coulomb expansion of pentacene layers, and the subsequent reaggregation leads to the chiral flipping of the supramolecular pinwheels and 2D domains. Our results provide a new strategy for dynamic control of the 2D chiral structures and help to steer the supramolecular assembly toward homochirality.