Frederick and Eleanor Little have a son, George Little. They want to find him a little brother to keep him company, so they visit New York City Orphanage in order to find a brother that is perfect. They look around at all the different children and they see it's inpossible to choose one. They see Stuart reading a book and he comments on how they know what each other are going to say. He wishes he can have a proper family and he says that nobody wants him.
The couple feel sorry for Stuart and give him a home with them. The woman at the orphanage warns them that the different species between mouse and humans will be a problem. They decide to take him anyway. Stuart is really happy to have a family and they tell him that he has a brother called George. He arrives home from school, and is excited to see a new little brother for him. It isn't what he expected and he is disappointed with Stuart, because he isn't human.
Stuart then meets Snowbell, the family cat, who doesn't take to him at all. The vicous tom cat is not happy with the situation of having a master who is a mouse. He doesn't want his friends to find out about this new arrangement. His cat friends will make fun of him, so he starts to hate Stuart more and more. Snowbell is jealous that Stuart Little is part of the family, and he is taking the family off him.
Whilist Stuart is trying his best to fit in, his looks and height seem to be a problem for him. He gets put in the washing machine by accident and nearly drowns.
The family go shopping together to buy Stuart a suit for a family gathering, to be introduced to the Little family. Stuart isn't what they expect but they cover it up and welcome him to the family. George and Stuart are given a ball to symbolise that they are brothers, this is when George speeks out, he says that Stuart isn't his brother and everybody leaves. Stuart is left there, feeling that there is something missing in his life - an empty space.
Snowbell is disliking Stuart more everyday, his friend Monty comes into his house looking for something to eat and Snowbell is trying to make him leave, so he doesn't see Stuart. Monty spots him in a cereal box and tried to eat him. Snowbell is angry because he knows Monty will reveal to the other cats, that a rat owns a cat!
Stuart goes into George's room and they finally play with each other and get along. George calls Stuart his friend but not his brother, but he is growing on him. Stuart gets in to a red roadstar car belonging to George, next Stuart sees a boat which George and his dad made. It isn't finnished because George is too scared to enter the race in 2 days as he is scared he will loose. Stuart helps to convince George and he says he will help him prepair the boat ready for the race. The whole family decide to finnish it together in order for it to be ready in time.
Snowbell meets up with some alley cats through his friend Monty, Smokey thinks up a plan to help get rid of Stuart, so Snowbell's life can be back to how it was, before he came along.
The family go to the boat race and a bully called Anton, tries to put George off the race by saying 'I'm glad you came, somebody has to loose.' George is worried about the race and wants to go home. Stuart tries to lift the remote and carry it ready for the race and he drops it, somebody stands on it and it boat wont work without the remote. Goerge is upset and Stuart thinks he has ruined everything. In order to make things better he sails the boat.
The family are worried because Stuart can't swim. George sees Anton again and gives back as good as he gets complete with a fight. Stuart wins the race and George finally admits that Stuart is his brother. They have a family photo and Stuart finally thinks he fits in. All is well but then there is a knock at the door, it is Stuart's proper parents there! they want him to go and live with them so they can be a family. After thinking it over, the Little's want what's best for Stuart and if he has an 'empty space' maybe he should go.
He does go, but it turns out that Stuart doesn't know it, but his real parents are dead and they are fakes, set up by the cats. The 'fake parents' get to like Stuart and tell him that they arn't his real parents. He leaves to go back home, greated by the unfriendly cats in the park. The family are missing Stuart so cut out the picture of him and make posters, they head to the park to put them up.
Stuart escapes the cats and goes home to an empty house, Snowbell is there and he turns Stuart against the family saying that they were at the movies celebrating his departure and they had removed his picture from the photo because they hate him. After a while Snowbell tells him the truth and they become friends. The family return and they are glad to have Stuart back with them.