By focusing on the way in which Edgar Allan Poe recognizes and represents some particular neuroscientific facts of human mind and agency, this essay examines what we can call Poe’s neuroscience in terms of his insight into neuroscientific posthumanism. In “Ligeia” Poe depicts how the brain perceives and cognizes facial features, voice, and the act of reading in its own signifying process. In “The Fall of the House of Usher” Poe’s narrator shows his sharp attention to the emotive mechanism and its functions. In “The Man of the Crowd” Poe captures the instances of the pattern recognition and subsequent abstract categorization of the brain, while in “William Wilson” he describes the case of fictional identification and its substantiation also taking place in the brain. All these examples indicate how Poe foreshadows the current neuroscientific notions of posthumanism, in which he focuses on representing how his characters fail to follow the rules of human and social evolution. This is, I argue in this essay, what is central to Poe’s posthumanism.