Abstract This article reports the design, modeling, and experiments of a novel retinal surgery robot based on spatial variable remote center-of-motion (RCM) mechanism. The general design criteria for parallel mechanisms are proposed, and the planar five-bar mechanisms are evaluated and selected. The planar-spatial evolution process, including the parallel connection of the planar mechanism and the equivalent substitution of joints, is adopted to develop a spatial variable RCM mechanism and then the robot. The mobility and singularity of the robot are analyzed, and the forward/inverse kinematics and workspace are modeled. Dimension optimization is conducted based on a comprehensive performance indicator that characterizes the motion range of linear actuators and the global dexterity performance index of robot. The prototyped robot is fabricated and assembled, and the kinematic calibration is performed. The position error of end-effector is within 34 μm, and both the position error and deviation of the RCM point are within 23 μm. The robot is demonstrated to reach the desired position and execute the RCM motion with high precision simultaneously.