Wilbur is the runt of a litter born to a pig on the farm of Fern Arable's father. When it is announced that her father is going to kill the pig, Fern rushes forth to save it, asking of her father: "If I had been very small at birth, would you have killed me?" Her father spares the pig, but only if Fern agrees to care for it. Falling in love immediately with the little pig, she feeds him regularly with a bottle, and names him Wilbur.

Wilbur is Fern's constant companion until he grows big enough to be transferred to his new home in the barn of Fern's neighboring uncle. Fern is able to visit Wilbur, but is unable to see him as often. Out of boredom, Wilbur begins to befriend other animals in the barn, who often patronizingly instruct the still naïve little pig in the ways of life. His most important friend, however, turns out to be a spider named Charlotte, who occupies a web in the corner of a doorway above him. Her love for Wilbur, coupled with her ingenuity, will save Wilbur's life.