Mazzola played 70 times for Italy between 1963 and 1974, scoring 22 goals. His debut for the national side was against Brazil on 12 May 1963, when he was aged only 20, and he marked the occasion by scoring a goal from a penalty. Mazzola later played for his country at the 1966 FIFA World Cup under Edmondo Fabbri, appearing in all three of Italy's group matches, and scoring in his nation's opening fixture, a 2–0 win over Chile, as Italy were eliminated in the first round; he later took part at the next two editions of the tournament with Italy. His biggest achievement with the national side came in 1968, however, when Italy won the 1968 European Championship on home soil under manager Ferruccio Valcareggi, and Mazzola was named as a member of the Team of the Tournament for his performance.