Fern Arable is an eight-year-old girl who lives on a farm with her parents and older brother Avery. One day, Fern stops her father from killing a runt pig, claiming it is unfair to kill the animal simply because it is small and weak. Fern names the pig Wilbur. For several weeks, Fern feeds Wilbur from a baby bottle and plays with him, and the two become close. But when Wilbur is five weeks old, Mr. Arable insists he must be sold. Fern calls her aunt and uncle, the Zuckermans, who also own a farm. They buy Wilbur for six dollars. Fern visits Wilbur in the Zuckerman barn often, but when she is not there, Wilbur feels bored and wants a friend. One day, a small voice says that it will be his friend. The voice belongs to Charlotte, a spider living on a web above Wilbur’s pen. Though Wilbur is happy to find a friend, he is disturbed by her bloodthirsty feeding habits. Overhearing their conversation, a goose in the barn thinks to herself that Wilbur doesn’t realize the Zuckermans will slaughter him at Christmas.

When summer arrives, Fern visits Wilbur almost every day, and the animals trust her. Wilbur is fed well and growing larger. One day, though, the oldest sheep tells Wilbur that the Zuckermans will soon kill him and make ham and bacon from him. Wilbur becomes terrified and cries out for someone to save him. Charlotte promises she will come up with a plan. Meanwhile, Fern tells her parents that she hears the animals at the Zuckermans’ barn talk, which deeply concerns her mother. After days of thinking, Charlotte decides she will play a trick on Mr. Zuckerman to save Wilbur. One night she tears a hole in her web and begins to spin. The next morning, when Lurvy, the Zuckermans’ farm hand, brings Wilbur’s slop to his trough, he notices Charlotte’s web above the pig. The words SOME PIG! are spelled out in the middle. Lurvy and the Zuckermans are astonished. Claiming the web is a miracle, Mr. Zuckerman tells the local minster. The news spreads, and people from all over the county come to see Wilbur.

Charlotte asks the barn animals to help her think of more words to write in her web. The goose suggests terrific. The oldest sheep persuades Templeton, the rat that lives under Wilbur’s trough, to tear out ads from newspapers in the dump and bring them to Charlotte for other words to use. That night Charlotte spins the word TERRIFIC in the middle of her web. Soon, people start returning to the Zuckerman farm to see the “terrific” pig. Mr. Zuckerman decides to bring Wilbur to the county fair in September. When Templeton brings a soap ad reading “With New Radiant Action” to Charlotte, she decides to spin RADIANT into her web. The next day, Fern tells her mother stories she has heard Charlotte tell Wilbur, including one about a cousin who spun a balloon and sailed away on the wind. Mrs. Arable drives into town to seek Dr. Dorian’s advice about her daughter’s behavior, but he assures her that eventually Fern will become just as interested in Henry Fussy, a boy she knows, as she is in the animals.

As the end of summer approaches, Charlotte writes RADIANT in her web, and crowds keep coming to see Wilbur. The Arables, the Zuckermans, and Lurvy prepare to go to the fair. Charlotte and Templeton hide themselves in the crate Lurvy built for Wilbur so they can go to the fair with him. Once there, Charlotte builds a web above Wilbur’s pen and notices a huge hog called Uncle next it. Soon after Fern and Avery run off to have fun, Fern meets Henry Fussy, who treats her to a roller coaster ride. Templeton goes off to the fair too and brings back a newspaper clipping with the word humble for Charlotte to write in her web. 

After a hot day at the fair, the families and Lurvy drive home. Charlotte is tired, but she tells Wilbur she is making a masterpiece that she will show him tomorrow. The next morning, Wilbur sees that Charlotte has made an egg sac with 514 eggs. Charlotte tells Wilbur she doesn’t think she will live to see her children. Templeton tells Wilbur and Charlotte that Uncle has a blue tag on his pen, meaning he won first prize.

Arriving at the fair, the Arables, the Zuckermans, and Lurvy spot the word HUMBLE in Charlotte’s web and rejoice, but then they notice that Uncle has already won. Mr. Zuckerman still insists on giving Wilbur a buttermilk bath to make him look his best. Suddenly a voice comes over the loudspeaker, announcing that a special award will be given and asking Mr. Zuckerman to bring his pig to the judges’ booth. On the way there, Fern sees Henry, and she races off to treat him to a Ferris wheel ride. Mr. Zuckerman is awarded $25 and a bronze medal. Wilbur faints in the excitement, but Templeton bites his tail to revive him. Back at Wilbur’s pen, Charlotte says she will not be returning to the farm because she will die soon. Wilbur promises Templeton that if he retrieves Charlotte’s egg sac, Wilbur will always let him eat from his trough first. Templeton agrees. Wilbur holds the egg sac in his mouth. As Wilbur is pushed into his crate, he winks at Charlotte, who whispers goodbye and waves. The next day, Charlotte dies.

Wilbur returns home with the egg sac. Throughout the winter, he guards and warms it, and in spring, tiny spiders begin crawling out. One morning, each young spider spins a balloon with fine silk and sails away on a warm draft. Wilbur cries himself to sleep; however, when he awakens, three tiny voices greet him. Three of Charlotte’s daughters have decided to stay to be Wilbur’s friends. Every spring, new spiders are born. Most fly away, but a few always stay. Wilbur lives a good, long life, but he never forgets Charlotte.