In recent years, considerable research efforts have been devoted to the development of wearable multi-functional sensing technology to fulfill the requirements of healthcare smart detection, and much progress has been achieved. Due to the appealing characteristics of flexibility, stretchability and long-term stability, the sensors have been used in a wide range of applications, such as respiration monitoring, pulse wave detection, gait pattern analysis, etc. Wearable sensors based on single mechanisms are usually capable of sensing only one physiological or motion signal. In order to measure, record and analyze comprehensive physical conditions, it is indispensable to explore the wearable sensors based on hybrid mechanisms and realize the integration of multiple smart functions. Herein, we have summarized various working mechanisms (resistive, capacitive, triboelectric, piezoelectric, thermo-electric, pyroelectric) and hybrid mechanisms that are incorporated into wearable sensors. More importantly, to make wearable sensors work persistently, it is meaningful to combine flexible power units and wearable sensors and form a self-powered system. This article also emphasizes the utility of self-powered wearable sensors from the perspective of mechanisms, and gives applications. Furthermore, we discuss the emerging materials and structures that are applied to achieve high sensitivity. In the end, we present perspectives on the outlooks of wearable multi-functional sensing technology.