Mrs. Frisby is a field mouse who lives in a small house. Her husband died, so she has to find food herself. However, her mouse, Timothy, is very, very, sick. She goes to a mouse named Mr. Ages who might have medicine to help Timothy.
Mrs. Frisby goes to Mr. Ages, and he gives her 3 packets of medicine, and he tells her that Timothy probably has pneumonia. She has to keep him warm and still.
Mrs. Frisby takes the shortcut home, but she has to go next to the cat, Dragon, that all animals fear. She finds a crow named Jeremy that is tied to a tree, and the cat will eat him if he doesn't escape. Mrs. Frisby risks her own life to free the crow by chewing through the strings, and he, in return, drops her off at her own house.
When she gets inside, all of her children are huddled around Timothy in his bed. She gives Timothy his medicine, and after all 3 packets, he is out of danger. However, it is the springtime which means that Mr. Fitzgibbons plow will come around, but Timothy is too weak to move around.
The tractor dies, and Mr. Fitzgibbon has to order a new piece. That gives Mrs. Frisby more time. She sees the cat looking at her, but he doesn't pounce. He is asleep, and she sees rats marching!
Mrs. Frisby meets Jeremy, and he gives her advice to meet with the Owl. He agrees to bring her there at 5 o'clock.
Jeremy arrives at 5, and he meets her family. He flies her to the Owl, but she is terrified the whole time. She enters the Owl's nest, and she tells him her problem.
Owl tells her that there is no way to save her house, but tells her that she must move. However, when he figures out that she is the wife of Jonathan Frisby, he tells her that she should go talk to the rats that live in the rosebush. He tells her that she must ask for Justin and Nicodemus.
She arrives home, and her children are all worrying. Timothy knows that Moving Day is near, but he doesn't think that he will be well enough to move yet. She goes to meet with the rat. She gets in and meets with a huge rat. He tells her to leave, but she stays. She gets in and meets with Nicodemus.
The rats have electricity, light bulbs, and elevators. Mrs. Frisby waits in the library for the meeting to be over. She sees on a white board, THE PLAN OF THE RATS OF NIMH. She reads the board and wonders what NIMH is. Isabell, another rat, comes in and Mrs. Frisby asks her what it is, but she doesn't know.
The rats have a plan to move the house to the safe side of the stone. However, Mrs. Frisby has to put sleeping powder in Dragon's food. She then learns that her husband died doing this.
While some rats go get the sleeping powder, Nicodemus tells her a story.
Nicodemus and his friend Jenner find a bag of food. They are about to eat, when a net swoops down and catches them. They are taken into a lab, with a total of 63 rats. The scientists inject something into their hips. The scientists are trying to study brains. One rat refuses to give up, and that is Justin.
The scientists make them learn how to read. Justin learns how to open his cage by reading the instructions. he goes out to explore. They figure out how to escape through the air ducts. However, there is a fan that blows away several of the smaller mice. There is a screen that prevents the rats from getting outside, but they unscrew the bolts and get outside. They go outside and live in a mansion during the winter.
Justin and Mr. Ages wder, but she must get home to her children. They decide that she will come back later to give the powder to Dragon. When she does, she gets captured.
She is left in a birdcage. Justin comes and helps her escape. They go and move the house with a pulley system. Her house is finally safe.
The rats leave because they will be killed by the exterminators. Mrs. Frisby eventually tells her children the whole story.