The impact of a two-piece tennis ball on a human head is simulated by using an established full body model and a newly constructed tennis ball model. The new tennis ball model is validated against existing experimental data. The frontal impact of a tennis ball on a human head at a velocity of 25 m/s is first studied as the baseline case. The effects of the impact location, velocity and angle as well as the ball spinning are then examined. It is revealed that the lateral impact results in a higher risk of head injury than the frontal and crown impacts. In addition, it is found that the impact force and von Mises stress in the skull, the intracranial pressure and first principal strain in the brain, and the translational and rotational accelerations at the center of gravity of the head all increase with the increase of the impact velocity. Moreover, the normal (90-degree) impact has the highest risk of head injury, which is followed by the 60-degree, 45-degree and 30-degree impacts. Further, it is observed that the spinning of the tennis ball has insignificant effects on the head response. The simulation results show that there will be no skull fracture or mild brain injury in the baseline case. However, traumatic brain injuries may occur after the impact velocity exceeds 40 m/s. The findings of the current study provide new insights into the risks of head injuries induced by tennis ball impacts.