Cyclists are vulnerable road users and often suffer head-neck injuries in car–cyclist accidents. Wearing a helmet is currently the most prevalent protection method against such injuries. Today, there is an ongoing debate about the ability of helmets to protect the cyclists’ head-neck from injury. In the current study, we numerically reconstructed five real-world car–cyclist impact accidents, incorporating previously developed finite element models of four cyclist helmets to evaluate their protective performances. We made comparative head-neck injury predictions for unhelmeted and helmeted cyclists. The results show that helmets could clearly lower the risk of severe (AIS 4+) brain injury and skull fracture, as assessed by the predicted head injury criterion (HIC), while a relatively limited decrease in AIS 4+ brain injury risk can be achieved in terms of the analysis of CSDM0.25. Assessment using the maximum principal strain (MPS0.98) and head impact power (HIP) criteria suggests that helmets could lower the risk of diffuse axonal injury and subdural hematoma of the cyclist. The helmet efficacy in neck protection depends on the impact scenario. Therefore, wearing a helmet does not seem to cause a significant neck injury risk level increase to the cyclist. Our work presents important insights into the helmet’s efficacy in protecting the head-neck of cyclists and motivates further optimization of protective equipment.