Accurate assessment of rolling resistance is important for wheelchair propulsion analyses. However, the commonly used drag and deceleration tests are reported to underestimate rolling resistance up to 6% due to the (neglected) influence of trunk motion. The first aim of this study was to investigate the accuracy of using trunk and wheelchair kinematics to predict the intra-cyclical load distribution, more particularly front wheel loading, during hand-rim wheelchair propulsion. Secondly, the study compared the accuracy of rolling resistance determined from the predicted load distribution with the accuracy of drag test-based rolling resistance. Twenty-five able-bodied participants performed hand-rim wheelchair propulsion on a large motor-driven treadmill. During the treadmill sessions, front wheel load was assessed with load pins to determine the load distribution between the front and rear wheels. Accordingly, a machine learning model was trained to predict front wheel load from kinematic data. Based on two inertial sensors (attached to the trunk and wheelchair) and the machine learning model, front wheel load was predicted with a mean absolute error (MAE) of 3.8% (or 1.8 kg). Rolling resistance determined from the predicted load distribution (MAE: 0.9%, mean error (ME): 0.1%) was more accurate than drag test-based rolling resistance (MAE: 2.5%, ME: −1.3%).