Abstract Laser interferometry-based sensing and measurement (LISM) technique was originally investigated to perform dynamic measurements of the end effector of a robot manipulator in motion. This technique can provide dynamic position measurements in real time and has high accuracy, large working space, high sampling rate and automatic target tracking. In this paper, a methodology using LISM technique is proposed to perform laser interferometry-based guidance (LIG) for accurate positioning of a robot manipulator in high precision manufacturing operations. The methodology utilizes the LISM apparatus to guide the robot's end effector to a desired location or along a desired path by directing the robot to follow the trajectory mapped by the laser beam. This is accomplished through the establishment of techniques for path generation, sensing and data acquisition and guidance error determination and compensation in the control algorithm. The algorithms for this methodology, together with the measurement and analysis techniques are described. A number of experiments are carried out to examine and validate the proposed LIG technique. Experimental results show that the established technique can effectively improve the positioning accuracy of the robot manipulator.