A voiceover representing Nathaniel Dawson in the future narrates the following sequence (this could also be spoken by a live actor on the stage as the action unfolds): Nathaniel crosses an expansive property and approaches the front door of the House of Usher. In the distance, a storm appears to be approaching. The voiceover explains that he and Roderick Usher had been colleagues in the medical research field, but that Roderick had disappeared some time ago, abandoning their work. Recently, Nathaniel had received an urgent letter from Roderick asking him to come right away. And thus, Nathaniel is just arriving to the House of Usher, his friend’s family estate.

Nathaniel notices the decayed and gloomy façade of the building and pulls out the letter and looks it over. He hears a voice calling his name and turns just as the doors swing open. After a moment’s hesitation, Nathaniel enters the building. Once inside the house, the doors swing shut behind him. The approaching storm will get closer and closer as the play proceeds.

Inside the building, the voiceover has ended and the building is dark. Nathaniel sees and hears no one and calls out. He passes an elaborate staircase in a grand hallway and, unbeknownst to him, a woman appears behind him and then quickly ascends the stairs. Nathaniel hears the movement and goes to investigate but does not catch sight of the woman. Suddenly a fire appears to ignite in a fireplace at the end of the grand hallway. Nathaniel approaches a sitting area near the fire, calling out to anyone who might be around. The woman watches from a mezzanine level above the hallway.

In the sitting area Roderick Usher rises from a winged back chair looking haggard, ill, and forlorn. Nathaniel expresses concern for Roderick’s condition and offers to secure transportation for both of them back to civilization so Roderick may be treated. Roderick repeatedly refuses to leave but offers no additional explanation. Exasperated, Nathaniel pours himself a drink of brandy and is surprised when Roderick turns down a glass, further implying the severity of his condition. Roderick then explains that instead of leaving, Nathaniel must send for their medical equipment and journals and continue their research at the house. When Nathaniel demands an explanation, Roderick rebuffs him, and suddenly the woman from before appears, approaching the two men from down the hall. Nathaniel is surprised by her appearance, but she takes no notice of him and locks her focus on Roderick, who tries desperately to get her to leave. The woman continues her approach and tells Roderick that she needs him. He tries to avoid her, but they momentarily touch, and it appears that they are both suddenly overcome by some force of ecstasy. Eventually they break apart, and Roderick begs her to leave and promises to come to her. She reluctantly exits, and Nathaniel notices that Roderick is in a heightened state with a racing heart. Roderick asks for a guitar lying nearby. As he plays the guitar, Nathaniel checks his vitals; they gradually return to normal. As he calms down, Roderick reveals that the woman is his sister Madeline and that his symptoms include incredibly acute senses that make it almost impossible to function. Madeline is also afflicted, but her symptoms are nearly the opposite. She can barely feel anything and often suffers from fainting spells. Roderick reveals that he returned to the family estate upon the recent death of their parents and that generations of his family have suffered from similar ailments. He tells Nathaniel that the true reason for his medical research was initially to treat Madeline, but now he is forced to include himself. Nathaniel says he understands Roderick’s ambition, as well as his reason for disappearing. He agrees to help and offers to send for everything they need to continue their work at the house the next day. Roderick thanks Nathaniel and offers to show him to a room for the night.
As the men leave the sitting area, Nathaniel realizes that there are tombs in the walls of the house. Roderick reveals that the Usher family has lived in the house for centuries and that during the time of the Red Death, his ancestors sequestered themselves on the estate to avoid the plague. They never left, not even to bury their dead, and thus they are “surrounded by Ushers.”

They reach the elaborate staircase and discover Madeline’s prone body collapsed on the floor of the upper landing. Roderick becomes upset saying that he should have gone to her sooner because of her fainting spells. Nathaniel examines Madeline and discovers that she is dead. Roderick breaks down, but when Nathaniel offers to help make arrangements for a service for her, Roderick surprises him by telling him that they need to inter her that night in a tomb in the house due to family tradition. Nathaniel reluctantly agrees when the distraught Roderick presses him for help. Roderick asks Nathaniel to carry Madeline because of his condition and says he will lead them to her vault for interment. Nathaniel agrees and picks her up, and together the men venture further into the house.

As they move towards the burial vault for Madeline, the voiceover commences again during the transition, sharing that Nathaniel began to marvel at the fact that there were no other branches of the Usher family and that the entire line remained in the house, either dead or alive.

Upon arriving at the vault, Nathaniel lays Madeline to rest in a coffin. Roderick insists that Nathaniel nail the coffin shut with spikes due to another family tradition. Once the coffin is sealed, they exit the vault, and Roderick asks Nathaniel to help him chain and lock the door. When Nathaniel asks why, Roderick says it’s for security from looters, since, with Madeline gone, he wants to return to the outside world to receive treatment and continue the research. Nathaniel agrees to make arrangements after the storm has passed. Roderick leads Nathaniel out of the vault area and a transition begins.

This transition covers a passage of time, during which the voiceover confesses that Nathaniel had difficulty sleeping and wound up wandering the house for some time. Eventually he settles into bed, but is restless.

The next scene opens with Roderick sitting in a chair as Nathaniel tosses and turns in the bed. Roderick begins singing a song on the guitar called The Haunted Palace. A lightning strike wakens Nathaniel, who is surprised to see Roderick in his room. Roderick claims to be stricken by grief from the passing of Madeline and wanted Nathaniel’s company and the music to sooth him. Nathaniel understands and encourages Roderick to play.

As Roderick plays, the storm outside rages and thunder rocks the house. Sounds appear to emanate from both outside and inside the house. Nathaniel initially reacts to the sounds outside, while Roderick seems to react to the sounds inside the house, and he stops singing the song. Eventually Nathaniel hears a loud sound coming from inside the house, and when he goes to open an adjoining door, Roderick desperately stops him, telling him that Madeline is out there and coming for him. When pressed for an explanation, Roderick reveals that Madeline was not dead but in a cataleptic trance that mimicked death. Nathaniel is appalled, and they hear the sounds of something approaching the door to the bedroom. Roderick reveals that during the years of the Red Death, when the Ushers locked themselves on the estate, they had to resort to incest to survive and propagate. Roderick believes that this has led to a kind of sentience embedded in the house that continues to drive the Ushers to incest. Nathaniel questions this logic, and Roderick reveals that, in fact, his and Madeline’s parents were twin siblings. Furthermore, Roderick tells Nathaniel that the house has caused their afflictions and that the only relief they receive comes from when he and Madeline physically touch. His plan was to have Nathaniel help him inter Madeline during one of her cataleptic trances so that, once sealed in her coffin, she would naturally suffocate. With Madeline dead, Roderick believed the house would “release him,” since he would be the only remaining Usher. But, according to Roderick, Madeline woke up prematurely and the house helped her escape the sealed vault in order to try and propagate with him again. Nathaniel calls all of this nonsense and accuses Roderick of summoning him to the house to help him murder Madeline. Roderick then theorizes that, in his heightened state, because of his absence from the house for so long, he would not survive copulating with Madeline and consequently believes that sex is the only way out for both he and his sister. Suddenly Madeline blasts into the room and Roderick screams for Nathaniel to leave. Nathaniel runs from the room as Madeline and Roderick fall into an embrace, and subsequently Roderick’s heart fails. The house begins to rumble and, as Nathaniel rushes to exit, the walls appear to crack and the spirits of the entombed Ushers fly out into the night.

Once outside, Nathaniel turns to watch the structure of the house collapse upon itself. The voiceover concludes that Nathaniel has kept the secret of that night to himself for the remainder of his life for fear people would think him mad. But now, with death upon him, a dying Nathaniel is recording all of the events of that night in a journal for people to read and to rid himself of the haunting memories of the House of Usher.