It was not immediately clear whether President Mattarella would dissolve Parliament or call early elections.
Draghi put in his papers after key coalition partners decided to boycott a confidence vote.
Mattarella’s office at the Quirinale Palace said the President had “taken note” of the resignation and asked Draghi to continue as caretaker prime minister.
Draghi’s government faced a crisis Thursday after members of his coalition that consisted of right, left and populists ignored his appeal to remain united to complete the legislature’s natural term and ensure the implementation of the European Union-funded COVID-19 pandemic recovery programme.