Born at the Royal Palace of Turin, she was the third daughter of Charles Emmanuel III, King of Sardinia and his second wife Polyxena of Hesse-Rotenburg.
Her maternal cousins included Victor Amadeus, Prince of Carignan and his younger sister the future princesse de Lamballe, both of which were born at the court of Savoy.
She founded, with Giovanni Battista Canaveri, a home in her native Turin for widows and destitute noble women "Convitto Principessa Maria Felicita di Savoia".
As Charles Emmanuel took little interest in the rule of what was left of his kingdom, he and Clotilde lived in Rome and then in Naples as guests of the wealthy Colonna family.
She died in Rome and was buried at the Royal Basilica of Superga overlooking Turin, the traditional burial place of the House of Savoy.