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Abstract Cable-driven serial robots have emerged with high potential for wide applications due to their compact size and low inertia properties. However, developing this type of robot encounters a motion coupling issue that the movement of one joint leads to the motion of other joints, resulting in complex control. In this paper, we proposed a novel approach for motion decoupling based on a noncircular pulley. The length change of the driving cable caused by the motion coupling problem is resolved by using the noncircular pulley. The calculation process of the profile for the noncircular pulley is illustrated in detail. An optimization process based on the brute force method is presented to identify the optimal parameters to minimize the compensation error. A cable-driven serial robot based on the decoupling method is prototyped for assessments. Experiments are conducted to evaluate the performance of the proposed motion decoupling method. The results reveal that the proposed method can effectively resolve the motion coupling issue by maintaining almost constant cable length with a maximum accumulative error only as 0.086 mm, demonstrating the effectiveness of the method.