The play opens in the bedroom of a hotel in St. Cloud, on the Gulf Coast of Florida. Williams writes, "The principal set-piece is a great double bed which should be raked towards the audience." A woman is asleep in the bed, and a young man is next to her, awake and wearing "the trousers of white silk pyjamas." The woman tosses and turns, as the young man, whose name is Chance, lights a cigarette. A black waiter, Fly, comes in with coffee service, and Chance combs his hair before going to the door, thanking Fly, and asking him to mix him some Bromo.
As Fly opens the windows slightly, a choir singing the "Hallelujah Chorus" can be heard somewhere, and Chance comments on the fact that he did not know it was Sunday. Fly tells him that the singing is coming from the Episcopal Church, and the bells are coming from the Catholic Church. When Fly reveals that he knows that Chance's last name is Wayne, Chance is surprised. Fly tells him that he used to wait tables in the Grand Ballroom when Chance came and danced with Boss Finley's daughter. Chance raises Fly's tip to $5 in exchange for his silence about ever having known him.
They are interrupted by someone named George Scudder outside the door. Soon enough, Scudder, a 36-year-old doctor, enters. He tells Chance that the assistant manager who checked Chance in called him that morning to let him know Chance was there. He asks Chance why he's come back to St. Cloud, and Chance replies, "I've still got a mother and a girl in St. Cloud," before telling him that he heard his mother was sick.
Scudder tells Chance that his mother died a few weeks earlier, and Chance wants to know why no one told him. "A wire was sent you three days before she died, at the last address she had for you which was General Delivery, Los Angeles," Scudder tells him. Scudder asks Chance if he got the letter he sent right after he last left town, which included an important "private matter," but Chance says he did not. Scudder tells him, "...A certain girl we know had to go through an awful experience, a tragic ordeal, because of past contact with you." Chance wants to know if the girl was someone named Heavenly, and Scudder implies that it is indeed Heavenly, but refuses to name names. He warns Chance that Heavenly's brother and father are angry with him and will come after him, advising him to leave town with the sleeping woman, whom he refers to as The Princess. "I think I ought to remind you that once long ago the father of this girl wrote out a prescription for you, a sort of medical prescription, which is castration," says Scudder.
Chance tells Scudder that he will not leave St. Cloud without Heavenly, when Scudder informs him that he is marrying Heavenly next month, before leaving abruptly. Rattled by this news, Chance calls his Aunt Nonnie and tells her where he's staying, but she hangs up on him. He then wakes Princess up, removing her eyemask. At first, she doesn't remember who he is and she feels short of breath. Quickly, Chance fetches a crocodile case and Princess helps him open it using the number combination. She insists that she's dying, when he opens the bag and pulls out an inhalator.
When she calms down, Princess scolds Chance for locking her inhalator away, and asks for a pink pill and a vodka. In the middle of pouring the vodka, Chance calls someone named Mr. Hatcher and references Princess's compromised state, referring to her as "Miss Alexandra Del Lago." She begs him not to use her real name, and insists that she wants to forget who she is, and he hangs up the phone. Chance plugs in a tape recorder on the floor near the bed without Princess seeing. When Chance calls Princess "plump lady," she asks if she's put on weight, and he tells her she has since the disappointment last month. She asks for her glasses, which he tells her she smashed up when she fell recently.
Princess asks how old Chance is and he tells her he's 29 and that he used to be the best-looking boy in the town of St. Cloud. When he hands her the remnants of her glasses, she looks him over, then touches him sensually. She asks him if he's her nurse, and he implies that he is paid to travel with her, as a kind of gigolo. As Chance holds her, she complains of her memory loss and tells him her name is the "Princess Kosmonopolis." She remembers being in Tallahassee, and Chance tells her they are staying at the old Royal Palms Hotel in St. Cloud, as gulls fly by outside. She asks Chance to help her to the window, and she describes what she sees, weeping as she looks at the ocean.
Going back to the bed, Princess asks Chance to fetch her a small pouch of hashish from under the bed. Suddenly, Princess turns to the audience and "intermittently changes the focus of her attention." She talks about aging as a starlet, the fact that many people told her that she could return to the screen or the stage because she was "an artist, not just a star whose career depended on youth." She talks about the fact that one can never really retire from being an artist, so she retired to the moon, where there is limited oxygen. She talks about the fact that people gasped at a close-up of her in a movie where she looked older. "I made the mistake of wearing a very elaborate gown to the premiere, a gown with a train that had to be gathered up as I rose from my seat and began the interminable retreat from the city of flames, up, up, up the unbearably long theatre aisle, gasping for breath and still clutching up the regal white train of my gown, all the way up the [...] length of the aisle"
Princess says, "At some point in your life, the thing that you lived for is lost or abandoned, and then...you die, or find something else." She asks Chance what the body of water outside their window is and he tells her it's the Gulf.
The playwright, Tennessee Williams, describes the actions of the play almost novelistically. The room and the characters are described in great detail in the stage directions, down to the kinds of lamps that might be found in the room to the handsomeness of Chance's face and body. Whereas many plays might leave out such details, Williams gives his reader a sense of the exact visual dimensions of the stage, a painstaking blueprint that a theater director and designer might use very carefully, or choose to diverge from.
No sooner have we been introduced to Chance, the main character in the play, then we learn about some of the painful difficulties of his life. He has returned to St. Cloud after a long time away, only to learn from Scudder that his mother—from whom he was mostly estranged—has died, and that he caused some kind of damage to his hometown lover the last time he was home. It is also implied that he is a gigolo of some kind, having traveled back to his hometown with an aging woman whom he refers to as The Princess. Thus we see that the characters and scenarios of the play are rather tawdry and tragic already. Tennessee Williams creates a world within the first few moments of the play that is filled with disappointment and drama.
Sexuality is very present within the narrative and dialogue of the play, even if it is not referred to explicitly. The first scene takes place in a lavish hotel room, and we see an older woman and a younger man who are sharing a bed. When Scudder enters, he makes reference to some kind of crime that Chance committed against a former girlfriend, and it seems to be of a sexual nature, either an unwanted pregnancy or a venereal disease. No one says this outright, however, as Scudder simply says, "I think I ought to remind you that once long ago the father of this girl wrote out a prescription for you, a sort of medical prescription, which is castration," and we understand that Chance's past is indecent in some way.
Chance's reputation in town has been additionally sullied by the fact that he is now working as a gigolo, a live-in houseboy for the troubled and eccentric Princess. She treats him like a pet, looking over his body with objectifying attention and footing the bill for their lavish experiences together. Their relation is as much about the transaction and Princess's power over Chance as it is about their sexual relationship. After surveying Chance's body, Princess orders him around capriciously, getting off on the power she holds over him.
We get more of a window into Princess's character in her curious, fanciful, and beautifully written monologue that she addresses directly to the audience. She explains that she has been a great actress, but that she is now an aging artist. She distinguishes between the role of actress and artist, suggesting that an artist can never adequately retire, since one's work is one's life. She says, "So I retired to the moon, but the atmosphere of the moon doesn't have any oxygen in it. I began to feel breathless, in that withered, withering country, of time coming after time not meant to come after...." In this monologue, she poeticizes her panic attacks and asthmatic tendencies, attributing them to her new residence on the moon. In a suspended theatrical space, a confidence between character and audience, she confesses that her troubles are wrapped up in life's work—her art and her image.