Roddy St. James is a decidedly upper crust pet rat who makes his home in a posh Kensington flat. When a common sewer rat named Sid comes spewing out of the sink and decides to stay, especially as England are playing Germany in the FIFA World Cup final, Roddy schemes to get rid of Sid by luring him into the "jacuzzi", which is actually the toilet bowl. Sid may be an ignorant slob, but being a sewer rat, he knows his plumbing. He plays along and instead pushes Roddy in and flushes him away into the sewer.
There, Roddy meets Rita Malone, an enterprising scavenger rat who works the drains in her faithful boat, the Jammy Dodger. Rita does not like Roddy initially, but ends up taking him along as The Toad sends his henchmen, Spike and Whitey, after her because she had stolen back her father's prized ruby a long time ago. The Toad despises all rodents to the point of hateful obsession, blaming rats for his fall from grace (he was once Prince Charles' pet). He decides to have them frozen with liquid nitrogen. However, The Toad's plan fails. Worse, during their escape, Rita takes a unique electrical cable. The cable is required to control the Floodgates. The Toad's evil plan is to open the gates during halftime of the World Cup, drowning the rats and their underground city in sewage. He can then use the depopulated city as a home for millions of his own tadpole offspring.
Roddy finds that the ruby is a fake and breaks it in front of Rita, enraging her, for she can now not get the money she needs for her large family. Roddy offers her a real ruby if she takes him back to Kensington. Accepting the offer, the pair first stop to visit her family before setting off. During Roddy's stay, he overhears a conversation that causes him to think that Rita had double-crossed him, so he steals the Jammy Dodger. When Rita catches up to him, he is able to clear up the misunderstanding.
The pair evade Spike and Whitey pursuing in a remote-controlled toy boat, with Thimblenose Ted and others on eggbeater jet skis. During this scene, Roddy and Rita share a quick love moment. Incensed at his minions repeated failures, The Toad sends to France for his cousin; an infamous, if somewhat laid back, mercenary known as Le Frog. Le Frog and his subordinates intercept the duo and retrieve the cable, but Roddy and Rita use a plastic bag to lift themselves out of the sewer (snatching away the cable during the ascent) and get Roddy home, though the Jammy Dodger has to be sacrificed.
Back home, Roddy pays Rita the promised ruby and an emerald, then proceeds to show her around his house. She at first believes he has family in the home, but noticing his cage, she realizes he's a pet. Roddy tries to pass Sid off as his brother, but Sid and Rita know each other. Rita tries to persuade Roddy to come with her, but he is too proud to admit that he is lonely. By now, they have fallen in love but have not told each other their feelings. She departs, both of them broken-hearted, but is soon captured by The Toad.
Talking to Sid about half-time, Roddy pieces together The Toad's plan. He gives Sid his cushy position and has Sid flush him back to the sewers to find Rita and save the city. Together, they defeat The Toad and freeze the wave of sewage generated by the flushing of countless toilets during the FIFA World Cup half-time with liquid nitrogen before it drowns the entire rat population.
Rita and Roddy build the Jammy Dodger Mark Two and set off in her with Rita's entire brood. A newspaper article reveals England had lost on penalties. Rita and Roddy become boyfriend and girlfriend. Later while the credits start, Roddy's former owner comes back with a new pet (a cat), which frightens Sid.