Hill-type muscle models are commonly used in musculoskeletal models to estimate muscle forces during human movement. However, the sensitivity of model predictions of muscle function to changes in muscle moment arms and muscle–tendon properties is not well understood. In the present study, a three-dimensional muscle-actuated model of the body was used to evaluate the sensitivity of the function of the major lower limb muscles in accelerating the whole-body center of mass during gait. Monte-Carlo analyses were used to quantify the effects of entire distributions of perturbations in the moment arms and architectural properties of muscles. In most cases, varying the moment arm and architectural properties of a muscle affected the torque generated by that muscle about the joint(s) it spanned as well as the torques generated by adjacent muscles. Muscle function was most sensitive to changes in tendon slack length and least sensitive to changes in muscle moment arm. However, the sensitivity of muscle function to changes in moment arms and architectural properties was highly muscle-specific;​ muscle function was most sensitive in the cases of gastrocnemius and rectus femoris and insensitive in the cases of hamstrings and the medial sub-region of gluteus maximus. The sensitivity of a muscle's function was influenced by the magnitude of the muscle's force as well as the operating region of the muscle on its force-length curve. These findings have implications for the development of subject-specific models of the human musculoskeletal system.