Background The brain region responsible for the initiation of K-complexes has not been identified to date. Objective To determine the brain region responsible for originating K-complexes. Methods We reviewed all 269 patients assessed for epilepsy surgery with intracranial electrodes and single pulse electrical stimulation (SPES) at King's College Hospital between 1999 and 2013. Intracranial EEG responses to electrical stimulation at orbitofrontal, frontal, cingulate, temporal and parietal loci were compared visually with each patient's K-complexes and the degree of resemblance was quantified. Results Among the 269 patients, K-complex-like responses were exclusively observed in all 6 patients who had depth electrodes in the cingulate cortex. In each patient, the stimulation site eliciting the response of greatest similarity to the patient's K-complex was located within the dorso-caudal anterior cingulate. The K-complex like responses were evoked when the patients were awake. Conclusion Our findings provide the first causal evidence that the cingulate gyrus initiates the widespread synchronous activity that constitutes the K-complex. The induction of K-complex-like responses during wakefulness suggests that the mechanisms required for the initiation of K-complexes are separate from those involved in sleep.