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Manual wheelchair users are predisposed to overuse injuries resulting from repetitive movement. This study comprehensively evaluates kinematics, dynamics, and energy during manual wheelchair propulsion at two distinct speeds, utilizing OpenSim. Four participants with paraplegia were instructed to propel a wheelchair at self-selected comfortable and fast velocities. A SmartWheel device was used to measure hand reaction forces and propulsion torque. Kinematics was monitored using 18 reflective markers and two clusters, captured by a Motion Analysis system with 12 cameras. Joint angles and torque curves for rapid and comfortable conditions were compared employing Statistical Parametric Mapping (SPM). The average speed attained by the subjects for the comfortable and fast velocities were respectively 1.26 ± 0.18 m/s and 2.41 ± 0.32 m/s. The fast velocity necessitated a higher propulsive torque (7.91 vs. 26.17 Nm, p < 0.05), tangential (24.25 vs. 84.30 N, p < 0.05), and radial forces (28.62 vs. 63.58 N, p < 0.05) exerted on the wheel. Compared with slow, fast velocity average power input from the arm to the wheel (20.57 vs. 113.48 W, p < 0.05) and the average system’s power gain during the propulsion phase (20.30 vs. 114.88 W, p < 0.05) were larger. However, the mechanical efficiency, calculated as the ratio between the two powers, was similar.