After a little girl named Fern Arable pleads for the life of the runt of a litter of piglets, her father gives her the pig to nurture, and she names him Wilbur. She treats him as a pet, but a month later, Wilbur is no longer small and is sold to Fern's uncle, Homer Zuckerman. In Zuckerman's barnyard, Wilbur yearns for companionship but is snubbed by the other animals. He is befriended by a barn spider named Charlotte, whose web sits in a doorway overlooking Wilbur's enclosure. When Wilbur discovers that he is being raised for slaughter, she promises to find a way to save his life. Fern often sits on a stool, listening to the animals' conversation, but over the course of the story, as she starts to mature, she begins to find other interests.
As the summer passes, Charlotte ponders how to save Wilbur and comes up with a plan. Reasoning that Zuckerman would not kill a famous pig, Charlotte weaves words and short phrases in praise of Wilbur into her web. Charlotte weaves the words Some Pig into the web, and the next morning, the farmhand Lurvy sees the web and runs to find Mr. Zuckerman. This makes Wilbur, and the barn as a whole, into tourist attractions, because many people believe the web to be a miracle. After the excitement dies down, Charlotte weaves the word Terrific into her web, beginning the cycle anew. To maintain the public's interest in Wilbur, Charlotte then tells Templeton, a barn rat, to get another word for the web. He goes to the dump and finds a laundry detergent ad with the word radiant, which she then weaves into her web. Fern's mother starts to get worried that Fern is spending too much time around the animals because she is telling her mother stories about the animals talking. Mrs. Arable then goes to visit Dr. Dorian, who persuades her that being among animals is natural and likely therapeutic for Fern.
Wilbur is eventually entered into the county fair, and Charlotte, as well as Templeton, accompany him. He fails to win the blue ribbon but is awarded a special prize by the judges. Charlotte weaves the last word into her web, Humble. Charlotte hears the presentation of the award over the public address system and realizes that the prize means Zuckerman will cherish Wilbur for as long as the pig lives and will never slaughter him for his meat. However, Charlotte, being a barn spider with a naturally short lifespan, is already dying of natural causes by the time the award is announced. Knowing that she has saved Wilbur, and satisfied with the outcome of her life, she does not return to the barn with Wilbur and Templeton and instead remains at the fairgrounds to die. However, she allows Wilbur to take with him her egg sac, from which her children will hatch in the spring. Meanwhile, Fern, who has matured significantly since the beginning of the novel, loses interest in Wilbur and starts paying more attention to boys her age. She misses most of the fair's events in order to go on the Ferris wheel with Henry Fussy, one of her classmates.
Wilbur waits out the winter, a winter he would not have survived but for Charlotte. He is initially delighted when Charlotte's children hatch but is later devastated when most leave the barn. There are only three remaining spiders. Pleased at finding new friends, Wilbur names one of them Nellie, while the remaining two name themselves Joy and Aranea. Further generations of spiders keep Wilbur company in subsequent years.
