In June 2021, he was included in Italy's squad for UEFA Euro 2020. In Italy's second group match against Switzerland in Rome on 16 June, Acerbi made his first appearance of the tournament, coming on for the injured Giorgio Chiellini in the first half of an eventual 3–0 victory, which allowed his side to advance to the knock-out stages. On 26 June, he started and assisted the match-winning goal, scored by Matteo Pessina, in extra-time of a 2–1 win over Austria in the round of 16. On 11 July, Acerbi won the European Championship with Italy following a 3–2 penalty shoot-out victory over England at Wembley Stadium in the final, after a 1–1 draw in extra-time.