Flexible memristor-based neural network hardware is capable of implementing parallel computation within the memory units, thus holding great promise for fast and energy-efficient neuromorphic computing in flexible electronics. However, the current flexible memristor (FM) is mostly operated with a filamentary mechanism, which demands large energy consumption in both setting and computing. Herein, we report an Ag2S-based FM working with distinct interface resistance–switching (RS) mechanism. In direct contrast to conventional filamentary memristors, RS in this Ag2S device is facilitated by the space charge-induced Schottky barrier modification at the Ag/Ag2S interface, which can be achieved with the setting voltage below the threshold voltage required for filament formation. The memristor based on interface RS exhibits 105 endurance cycles and 104 s retention under bending condition, and multiple level conductive states with exceptional tunability and stability. Since interface RS does not require the formation of a continuous Ag filament via Ag+ ion reduction, it can achieve an ultralow switching energy of ∼0.2 fJ. Furthermore, a hardware-based image processing with a software-comparable computing accuracy is demonstrated using the flexible Ag2S memristor array. And the image processing with interface RS indeed consumes 2 orders of magnitude lower power than that with filamentary RS on the same hardware. This study demonstrates a new resistance–switching mechanism for energy-efficient flexible neural network hardware.