Muscles actuate running by developing forces that propel the body forward while supporting the body’s weight. To understand how muscles contribute to propulsion (i.e., forward acceleration of the mass center) and support (i.e., upward acceleration of the mass center) during running we developed a three- dimensional muscle-actuated simulation of the running gait cycle. The simulation is driven by 92 musculotendon actuators of the lower extremities and torso and includes the dynamics of arm motion. We analyzed the simulation to determine how each muscle contributed to the acceleration of the body mass center. During the early part of the stance phase, the quadriceps muscle group was the largest contributor to braking (i.e., backward acceleration of the mass center) and support. During the second half of the stance phase, the soleus and gastrocnemius muscles were the greatest contributors to propulsion and support. The arms did not contribute substantially to either propulsion or support, generating less than 1% of the peak mass center acceleration. However, the arms effectively counterbalanced the vertical angular momentum of the lower extremities. Our analysis reveals that the quadriceps and plantarflexors are the major contributors to acceleration of the body mass center during running.