Manipulability quantification and evaluation of robot manipulators plays an important role in robotic mechanism design, motion planning, and control. In this article, a general methodology of using manipulability polytopes to characterize the manipulator’s capability to generate velocities, forces, and accelerations at the end-effector is proposed. This methodology can be used to determine the kinematic, mechanical, and dynamic manipulability of both redundant and nonredundant serial manipulators, where influences of gravity, joint velocities and accelerations, and end-effector payload on the dynamic manipulability are incorporated into the derivation of the manipulability polytopes. Since the manipulability polytope is the feasible region defined by all the joint constraints, the proposed method is suitable for solving the problems including both symmetric and asymmetric joint constraints. Furthermore, a systematic architecture and detailed procedures for performance computation with respect to different types of manipulability of serial robot manipulators are presented. Two typical application examples, respectively, for two and three degree-of-freedom planar manipulators are given to illustrate the correctness and capability of the proposed methodology.