Active exoskeletons are promising devices for improving rehabilitation procedures in patients and preventing musculoskeletal disorders in workers. In particular, exoskeletons implementing human limb’s weight support are interesting to restore some mobility in patients with muscle weakness and help in occupational load carrying tasks. The present study aims at improving weight support of the upper limb by providing a weight model considering joint misalignments and a control law including feedforward terms learned from a prior population-based analysis. Three experiments, for design and validation purposes, are conducted on a total of 65 participants who performed posture maintenance and elbow flexion/extension movements. The introduction of joint misalignments in the weight support model significantly reduced the model errors, in terms of weight estimation, and enhanced the estimation reliability. The introduced control architecture reduced model tracking errors regardless of the condition. Weight support significantly decreased the activity of antigravity muscles, as expected, but increased the activity of elbow extensors because gravity is usually exploited by humans to accelerate a limb downwards. These findings suggest that an adaptive weight support controller could be envisioned to further minimize human effort in certain applications.