Dexterous control of upper limb prostheses with multiarticulated wrists/hands is still a challenge due to the limitations of myoelectric man–machine interfaces. Multiple factors limit the overall performance and usability of these interfaces, such as the need to control degrees of freedom sequentially and not concurrently, and the inaccuracies in decoding the user intent from weak or fatigued muscles. In this article, we developed a novel man–machine interface that endows a myoelectric prosthesis (MYO) with artificial perception, estimation of user intention, and intelligent control (MYO–PACE) to continuously support the user with automation while preparing the prosthesis for grasping. We compared the MYO–PACE against state-of-the-art myoelectric control (pattern recognition) in laboratory and clinical tests. For this purpose, eight able-bodied and two amputee individuals performed a standard clinical test consisting of a series of manipulation tasks (portion of the SHAP test), as well as a more complex sequence of transfer tasks in a cluttered scene. In all tests, the subjects not only completed the trials faster using the MYO–PACE but also achieved more efficient myoelectric control. These results demonstrate that the implementation of advanced perception, context interpretation, and autonomous decision-making into active prostheses improves control dexterity. Moreover, it also effectively supports the user by speeding up the preshaping phase of the movement and decreasing muscle use.