The advancement of smart textiles has resulted in significant development in wearable textile sensors and offers novel interfaces to sense physical movements in daily life. Knitting, as a traditional textile fabrication method, is being used in promising ways to realize fully seamless fabrication and unobtrusive sensing in wearable textile applications. However, current flat-knitted sensors can sense strain only in the horizontal plane. This research presents a novel fully machine-knitted spacer piezoresistive sensor structure with a three-directional sensing ability that can detect both the pressure in the vertical direction and the strain in the warp/weft direction. Besides, it can sense the pressure under 1 kPa, which is critical in comfortable on-body interaction, one-piece integration, and wearable applications. Three sizes spacer-knitted sensors are evaluated in terms of their mechanical performance, stability cycles, and reaction to external factors such as sweat, laundering, etc. Then, the effect of material choice on sensor performance is evaluated and the rationale behind the use of different materials is summarized. Specifically, this research presents a detailed evaluation of the applications with both a single sensor and multiple sensor arrays for fine and gross motion sensing in several scenarios. The testing results demonstrate a fully machine-knitted piezoresistive sensor that can detect multidirectional motions (vertical, warp, and weft directions). In addition, this knitted sensor is scalable and can be facilely and seamlessly integrated into any garment piece. This universal knitted sensor structure could be made with a wide variety of materials for high sensitivity for multidirectional strain/pressure sensing, making it a high-compatibility sensor structure for wearable applications.