Smart materials with controllable responses to various stimulations offer considerable potential in many applications. Herein we report a simple and efficient method to fabricate ionic strength- and thermo-responsive polyethersulfone composite membranes using zwitterionic copolymers of sulfobetaine methacrylamide (SBMI) and sulfobetaine methacrylate (SBMA). The permeability of the modified membranes could be adjusted by varying the ionic strength from 0 mol kg⁻¹ to 1.0 mol kg⁻¹ and/or varying the surrounding temperature from 15 °C to 90 °C, and both the responses were reversible. The thermo-response transition temperature could be regulated by changing the chemical compositions of the zwitterionic copolymers. Furthermore, the zwitterionic copolymer modified membranes exhibited excellent antifouling resistances to protein solutions and surfactant-stabilized oil-in-water emulsions. Their ionic strength- and thermo-responsive flux, separation ability, and excellent antifouling properties endowed the membranes with a wide range of applications in the field of separation.