A widowed field mouse must move her family -- including an ailing son -- to escape a farmer's plow. Aided by a crow and a pack of superintelligent, escaped lab rats, the brave mother struggles to transplant her home to firmer ground.

The rats and mice, made intellectually superior in the original Secret of N.I.M.H., return to Thorn Valley to groom their destined leader - young Timmy Brisby.

A young mouse named Fievel and his family decide to migrate to America, a "land without cats," at the turn of the 20th century. But somehow, Fievel ends up in the New World alone and must fend off not only the felines he never thought he'd have to deal with again but also the loneliness of being away from home.

Some time after the Mousekewitz's have settled in America, they find that they are still having problems with the threat of cats. That makes them eager to try another home out in the west, where they are promised that mice and cats live in peace. Unfortunately, the one making this claim is an oily con artist named Cat R. Waul who is intent on his own sinister plan.