Waterproof fiber-based strain sensors with a high gauge factor and outstanding stability are essential for smart textiles, wearable devices and biomedical electronics. In this work, we demonstrate a highly flexible, stretchable, sensitive, and waterproof core-sheath structure strain sensor with a relatively wide strain-sensing range fabricated by a simple approach. Such a core-sheath structure is composed of a superelastic core material polyurethane (PU) yarn; a highly conductive multilayer sheath material, namely, graphene nanosheets/thin gold film/graphene nanosheets (GNSs/Au/GNSs); and a thin polydimethylsiloxane (PDMS) wrapping layer. The combination of the PU yarn, multilayer GNSs/Au/GNSs, and PDMS wrapping layer enables the strain sensor to achieve high flexibility and stretchability, high sensitivity, broad strain-sensing range, and good waterproof property simultaneously due to the infiltration of PDMS into the multilayer during stretching. Particularly, the yarn strain sensor exhibits a high gauge factor (GF: 661.59), outstanding stability with an applied strain of 50% for approximately 10 000 stretch/release cycles, and superior water resistance. Moreover, it can be readily integrated into textiles, including medical textile bandages and textile gloves, for monitoring various human motions (e.g., phonation, pulse, finger bending, and walking) and effectively control a hand robot. Therefore, strain sensors show considerable potential in textile, wearable, and biomedical electronics for healthcare-related applications, such as disease diagnosis, preventive healthcare, and rehabilitation care, and robot controlling-related applications (e.g., controlling a hand robot to catch some objects).