The book opens in conversation, as Mr. Shelby, a well-mannered plantation owner described as being of average character, with good nature and kindness, discusses the potential sale of his trustworthy servant, Uncle Tom, to Haley, a slave trader. Mr. Shelby’s Kentucky plantation is performing poorly, leaving him in dire financial straits; he hopes that the sale of Uncle Tom will be enough to repay his debt. 

Speaking to Haley, Mr. Shelby praises Tom's hardworking nature and religious beliefs. However, Tom’s good qualities do not persuade the slave trader; Haley wants to add more enslaved individuals to the sale to repay his debt. During the negotiations, Little Harry, a young slave, amuses the men with his singing and dancing. Eliza, Harry's mother and a servant to Mrs. Shelby, comes to take him away. After their departure, Haley tries to convince Mr. Shelby to sell both Eliza and Harry. Mr. Shelby refuses to sell Eliza due to his wife's attachment to her but is receptive to the idea of selling Harry.

As she carries Harry away, Eliza overhears Mr. Shelby telling Haley he might be willing to part with Harry. Distraught, she shares her fears with Mrs. Shelby. Unfortunately, Mrs. Shelby is unaware of her husband's financial difficulties and mistakenly assures Eliza that she and Harry will be safe. Throughout the scene, Mrs. Shelby is depicted as an intelligent and moral high-class woman.