A silicon-on-insulator (SOI) piezoresistive three-axis acceleration sensor, consisting of four L-shaped beams, two intermediate double beams, two masses, and twelve piezoresistors, was presented in this work. To detect the acceleration vector (ax, ay, and az) along three directions, twelve piezoresistors were designed on four L-shaped beams and two intermediate beams to form three detecting Wheatstone bridges. A sensitive element simulation model was built using ANSYS finite element simulation software to investigate the cross-interference of sensitivity for the proposed sensor. Based on that, the sensor chip was fabricated on a SOI wafer by using microelectromechanical system (MEMS) technology and packaged on a printed circuit board (PCB). At room temperature and VDD = 5.0 V, the sensitivities of the sensor along x-axis, y-axis, and z-axis were 0.255 mV/g, 0.131 mV/g, and 0.404 mV/g, respectively. The experimental results show that the proposed sensor can realize the detection of acceleration along three directions.