The wetting behavior of hierarchically wrinkled surfaces has attracted great interest because of its broad application in flexible electronic, microfluidic chip, and biomedicine. However, theoretical studies concerning the relationship between the apparent contact angle and mechanical strain applied on the soft and flexible surface with a hierarchically wrinkled structure are still limited. We established a theoretical framework to describe and understand how prestrain and applied dynamic strain reversibly tune the wettability of the hierarchically wrinkled surface. More specifically, a direct relationship between the mechanical strain and contact angle was built through reversible tuning of the amplitude and the wavelength of the wrinkled structures caused by mechanical strain, which allowed for more precise adjustment of surface wettability. To verify the accuracy of the theoretical relationship between the contact angle and mechanical strain, a soft surface with a hierarchically wrinkled structure was prepared by combining wrinkled microstructures and strip ones. The results showed that the experimental contact angles were in agreement with the theoretical ones within a limited error range. This will be helpful for further investigation on the wettability of hierarchically wrinkled surfaces.