When heated, insects lose coordinated movement followed by the onset of heat coma (critical thermal maximum, CTmax). These traits are popular measures to quantify interspecific and intraspecific differences in insect heat tolerance, and CTmax correlates well with current species distributions of insects, including Drosophila. Here, we examined the function of the central nervous system (CNS) in five species of Drosophila with different heat tolerances, while they were exposed to either constant high  temperature or a gradually increasing temperature (ramp). Tolerant species were able to preserve CNS function at higher temperatures and for longer durations than sensitive species, and similar differences were found for the behavioural indices (loss of coordination and onset of heat coma). Furthermore, the timing and temperature (constant and  ramp exposure, respectively) for loss of coordination or complete coma coincided with the occurrence of spreading depolarisation (SD) events in the CNS. These SD events  disrupt neurological function and silence the CNS, suggesting that CNS failure is the primary cause of impaired coordination and heat coma. Heat mortality occurs soon after heat coma in insects; to examine whether CNS failure could also be the proximal cause of heat death, we used selective heating of the head (CNS) and abdomen (visceral  tissues). When comparing the temperature causing 50% mortality (LT50) of each body part versus that of the whole animal, we found that the head was not particularly heat sensitive compared with the abdomen. Accordingly, it is unlikely that nervous failure is the principal/proximate cause of heat mortality in Drosophila.