De animatieserie speelt zich af in het heden. In het dorp Prostokvashino wonen de kat Matroskin en de hond Sharik, die bezoek krijgen van oom Fyodor. Hij heeft een jongere zus, Vera Pavlovna. Een nieuw personage verschijnt in Prostokvashino: het knaagdier Tama-Tama, dat de vriend van Vera Pavlovna wordt.

It seemed that no storms of the outside world could shake the usual and measured course of village life in Prostokvashino. Time seemed to freeze. Still, every morning Matroskin tastes fresh milk obtained from his pet cow Murka. The Ball still spends time in the surrounding forests, "photo hunting" for rare game. However, now he has learned how to post photos of his prey on the Internet. And still, Uncle Fyodor visits them at every opportunity. And then they have fun and amicably spend time with their male company. And when it began to seem to them that this would always be the case, suddenly everything changed with the appearance of one little girl, Uncle Fyodor's own sister. And the name of this girl is Vera Pavlovna.

Действие мультсериала происходит в наши дни. В деревне Простоквашино живут кот Матроскин и пёс Шарик, которых навещает Дядя Фёдор. У него появляется младшая сестра — Вера Павловна. В Простоквашино появляется новый персонаж — зверёк-грызун Тама-Тама, который становится другом Веры Павловны.