One morning at the breakfast table, eight year old Fern sees her father leave the house with an axe and asks her mother where he's going. Her mother delivers the shocking news that Mr Arable is going out to kill a runt that was born the night before. Fern chases her father down and persuades him to spare the runt, telling him that it is unjust to kill a piglet just because it is small. Moved by his daughter's plea, Mr Arable decides to give the runt to her to look after.
Fern names the piglet Wilbur and looks after him like a baby, pushing him in her pram alongside her doll and feeding him with a bottle. At five weeks old Mr Arable insists that Wilbur is sold and he goes to live in the Zuckerman barn down the road.
Wilbur initially struggles at the barn because he misses Fern so much but soon he becomes acquainted with new friends, the best of whom is a lady grey spider called Charlotte. Wilbur is fascinated by Charlotte, although to begin with he is slightly suspicious of the way she catches her food - he doesn't like the idea that she spins bugs in her web and sucks their blood. He soon realizes that Charlotte is everything but cruel and bloodthirsty and that her method of eating is entirely necessary for a spider.
Wilbur is complete happy during the summer days - Fern comes to visit and his new friend tells him exciting stories and has the patience to try and coach him about how to spin a web (although she knows fine well he will never be able to) but one day he gets some terrible news that puts an end to his carefree attitude.
The sheep tells Wilbur that Mr Zuckerman is fattening him up for Christmas dinner and Wilbur is distraught - he is so happy on the farm and doesn't want to die. Charlotte calms him down and promises him that she won't let him be killed. She hasn't worked out how to save him yet, but she is determined that she will.
One morning as Lurvy pours Wilbur's slops, he notices Charlotte's twinkling spider web in the morning fog. The words 'SOME PIG' have been weaved into the web. Lurvy is gobsmacked and utters a prayer. He quickly tells Mr Zuckerman who is equally amazed and soon the news spreads near and far.
Worried that people may be getting bored of 'SOME PIG', Charlotte asks Templeton the rat to aid her in finding more words to write in her web. Knowing that if Wilbur is killed he won't have access to his slops, Templeton reluctantly scavenges for newspaper clippings to help Charlotte. The next word she writes is 'TERRIFIC' and after that, 'RADIANT.'
Meanwhile, Mrs Arable is concerned that Fern is spending too much time down at the barn and becomes even more alarmed when her daughter tells her about Charlotte and the stories Charlotte tells. Mrs Arable decides to go and see Dr. Dorian to ask him what he makes of Fern thinking the animals can talk and what he makes of the mysterious writing in the web. Dr Dorian is very calm and rational and says that the real miracle is not the writing in the web but the fact that a spider instinctively knows how to build a web without any tuition. He says that it is quite possible that animals can talk and that the reason that adults cannot hear them might be because they talk too much to hear what is going on in nature.
With the news of Zuckerman's famous pig spreading, the Zuckermans and Arables decide to take Wilbur to the County Fair. Charlotte agrees to go too although she is feeling tired and soon has to build a sac to hold her eggs. At the fair, Charlotte is disappointed to see that beside Wilbur's pen is a much larger spring pig called Uncle. Knowing he is fierce competition, Charlotte decides to spin another web and once again Templeton is sent off to find a word.
The adults and children enjoy themselves at the fair and Avery and Fern are particularly excited that they are allowed to go off without their parents all afternoon. Fern spends all afternoon with Henry Fussy and they go on the Ferris wheel together. For months after, Fern will look back nostalgically at her time on the Ferris wheel with Henry.
Before nightfall Charlotte weaves her web with the new word 'HUMBLE' written into it and throughout the night she makes her egg sac. In the morning the Zuckermans and Arables see the web but they also notice that Uncle has a blue tag on his pen - he has already won first prize. Mr Zuckerman ignores the tag and tells everyone to buck up and give Wilbur a buttermilk bath. Everyone who comes to Wilbur's pen has something good to say about him.
Suddenly, over the loudspeaker a voice is heard asking Zuckerman to bring his famous pig to the judges' booth for a special award. Wilbur is awarded a medal for being phenomenal and completely out of the ordinary and Mr Zuckerman is given $25. Since the writing first appeared in the web, the miracle has been on everyone's mind. After the press photos and the commotion, Wilbur is returned to his pen.
Wilbur notices that Charlotte is quiet and looks unwell. She tells him that she is content now that she knows he is safe - she knows Mr Zuckerman will never harm him now, but she tells Wilbur that she is failing and will be dead in a day or two. Panicked and distraught Wilbur races around the pen, begging Charlotte to come home with him, but she hasn't enough energy to move. Wilbur decides to take Charlotte's egg sac and promises Templeton first choice of his slops if he retrieves the sac. As Wilbur carries the sac in his mouth and is led into the crate, he winks at Charlotte and she musters all the energy she can to wave goodbye. The next day, as the Ferris wheel is being taken apart, Charlotte dies.
Back at the Zuckerman’s, Wilbur is given a noisy welcome home. He waits patiently for the birth of Charlotte's children and often looks longingly at her empty, broken web. When her children are finally born, Wilbur is distraught to see them let out loose clouds of fine silk that carries them far away on the breeze. Three of Charlotte's children stay in the barn with Wilbur, however and become his good friends. Year after year new spiders are born to replace the old but no one ever replaces Charlotte in Wilbur's heart.