This study aimed to clarify the pathway mediating hyperthermia-induced alterations in neural drive transmission and determine if heat acclimation protects voluntary muscle activation and cognitive function in hyperthermic humans. Electrically evoked potentials (H reflex and M wave), executive function (special planning and working memory), and maximal voluntary isometric contractions (120 s) were assessed in 14 participants in control conditions [CON, 24°C, 40% relative humidity (RH)] and in a hyperthermic state (HYP, 44-50°C, 50% RH) on consecutive days in a counterbalanced order. Thereafter, participants were passively heat acclimated for 11 days (1 h per day, 48-50°C, 50% RH) before repeating the initial assessments. Heat acclimation decreased rectal temperature in CON (-0.2°C, < 0.05), but participants were maintained at ~39°C in HYP. Heat acclimation increased the time required to reach 39°C (+9 min), along with sweat rate (+0.7 l/h), and serum extracellular expression of heat shock protein 72 (eHSP72; +20%) in HYP ( < 0.05). M-wave and H-reflex amplitudes were lower in HYP than CON ( < 0.05) and were not protected by heat acclimation. Nerve conduction velocity was faster in HYP than CON ( < 0.05) without being influenced by heat acclimation. These results suggest that peripheral neural drive transmission in the hyperthermic state is primarily affected by axonal conduction velocity rather than synaptic failure. Executive function, voluntary activation, and the ability to sustain torque were impaired in HYP ( < 0.05). However, despite no perceptual changes ( > 0.05), heat acclimation restored executive function, while protecting the ability to sustain voluntary activation and torque production during a prolonged contraction in hyperthermia ( < 0.05). Ultimately, heat acclimation induces beneficial central but not peripheral neural adaptations. Heat acclimation restores planning accuracy and working memory in hyperthermic humans, together with the supraspinal capacity to sustain motor drive during a sustained maximal voluntary contraction. Electrically evoked potential data (M wave, H reflex) indicate that heat acclimation does not protect against hyperthermia-induced impairments in peripheral neural drive transmission. Heat acclimation induces beneficial central but not peripheral neural adaptations.