Duchess is the beloved pet cat of Madame Adelaide Bonfamille. She is the mother of three kittens, Berlioz, Marie, and Tolouse, and devotes much of her time to educating them in etiquette.
When the family butler, Edgar, drugs them in a plot to remove them from Bonfamille's will, Duchess and her kittens find themselves lost in the country.
They soon encounter Tom O'Malley, an alley cat, who, with the aid of Abigail and Amelia Gabble, twin geese, make their way back to Paris.
Edgar discovers the cats before Bonfamille can learn of their return, and he tosses them in a sack, planning to ship them off to Timbuktu. It is only with the help of Tom, his alley cat friends, Roquefort (a mouse), and Frou-Frou (a horse) that they manage to escape the trunk stamped for delivery, replacing themselves with Edgar.
Shortly thereafter, she and Tom become the cat-equivalent of spouses, and live among the other cats in Bonfamille's cat-friendly foundation.