Cognition depends on rapid and robust communication between neural circuits spanning different brain areas. We investigated the mesoscopic network of cortico-cortical interactions in the human brain in an extensive dataset consisting of 6,024 h of intracranial field potential recordings from 4,142 electrodes in 48 subjects. We evaluated communication between brain areas at the network level across different frequency bands. The interaction networks were validated against known anatomical measurements and neurophysiological interactions in humans and monkeys. The resulting human brain interactome is characterized by a broad and spatially specific, dynamic, and extensive network. The physiological interactome reveals small-world properties, which we conjecture might facilitate efficient and reliable information transmission. The interaction dynamics correlate with the brain sleep/awake state. These results constitute initial steps toward understanding how the interactome orchestrates cortical communication and provide a reference for future efforts assessing how dysfunctional interactions may lead to mental disorders.