Heat waves are increasingly common in subcontinent countries, including Pakistan. Heat stroke (HS) is a critical condition resulting from extreme temperatures, often culminating in multiorgan dysfunction. Clinical manifestations of heat-related emergencies can include altered mentation, fever, and profound weakness. We present a compelling case of a previously healthy 49-year-old male who developed altered mentation, fever, and acute kidney injury following intense physical exertion amidst a severe heat wave. Although initially managed as heat stroke, the patient soon exhibited dysarthria, palatal weakness, and bilateral lower limb weakness with areflexia, prompting a detailed neurological assessment. Electromyography and nerve conduction studies revealed the acute motor-sensory axonal neuropathy (AMSAN) variant of Guillain-Barré Syndrome (GBS), an uncommon but severe sequel of heat stroke. GBS, an autoimmune disorder, typically presents with ascending bilateral lower limb flaccid paralysis, often following an acute infectious trigger. Treatment with plasmapheresis led to remarkable neurological recovery. This case represents the first documented instance of heat stroke-induced GBS in Pakistan, highlighting both the distinctive clinical features and the therapeutic complexities of this rare condition.