After settling in America, the Mousekewitz family discovers that they still face the threat of cats. They are eager to try another home in the west, where they believe that mice and cats can coexist peacefully. Unfortunately, their new home is a shady character named Cat R. Waul, who is determined to fulfill his own sinister plan. Unaware of this, the Mousekewitz's begin their journey west, while their true cat friend, Tiger, follows intent on following his girlfriend, who has gone in the same direction.