Abstract: This study aims to improve the automation and intelligence of high-clearance sprayers, while avoiding pesticide poisoning to operators. An unmanned high-clearance sprayer was therefore developed and then manufactured using state-of-the-art autonomous navigation, mechanical, electrical, and hydraulic technologies. A conventional high-clearance booming sprayer was selected to serve as the platform. The electrical system of the sprayer was composed of five sub-systems, including the driving control, navigation, remote control, spraying, and ground station. Electric devices were designed to realize automatic control of engine start/stop, four-wheel steering, throttle aperture, moving speed, spraying pump, and booming beams. A micro-controller PIC18F258 with CAN and serial ports was utilized to process data, and then send signals to the relays and motor drivers that rotated DC motors as executors. An electric steering was also developed, including the brushless motor, potentiometer, motor driver, and steering controller. The brushless motor was used to provide the steering torque, where the output shaft of the motor was connected directly to the input shaft of the hydraulic steering unit. A CAN-bus communication network was established to allow for the real-time switch between two modes, such as remote control and autonomous navigation. A dual-antenna RTK-GNSS receiver and an Inertial Measurement Unit (IMU) were used as navigation sensors to collect the positioning and attitude data. An attitude-based correction was proposed to compensate positioning measurements corrupted by the chassis inclination, thereby accurately acquiring the actual position of the sprayer. The RTK-GNSS positioning data was also utilized to calculate the actual minimum turning radius during the headland turn, particularly considering kinematic characteristics in fields with various soil conditions. A straight path also needed to be planned according to the turning radius, in order to ensure the explicit turning trajectory and accurate path tracking after finishing the headland turn. The reason was that the distance between adjacent working paths was considerably larger than that of the turning radius, where the working width was 12 m. An automatic calibration was introduced to determine the range of steering angle, steering angle in straight and heading measurement shift for the high-accuracy driving. The correction was also necessary to consider the installation of GNSS antennas and the potentiometer on different fixing locations with respect to the machine body. As such, a comprehensive validation was gained on the automatic operating mechanisms and CAN-bus network communication. A series of experiments were also conducted to evaluate the performance of newly-developed unmanned high-clearance sprayers under remote control and autonomous navigation, in terms of automatic operation in path tracking. The results showed that the maximum values were 20.81 and 8.84 cm under the remote control and autonomous navigation, with the average errors of 0.90 and 3.16 cm on the left, and the maximal root mean square errors of 7.47 and 2.66 cm, respectively, in terms of the lateral error, indicating that the executing mechanisms responded to operation commands in a stable and rapid way. The driving performance under autonomous navigation was much better than under remote control in agricultural spraying.