Internationally, De Sisti earned 29 caps and scored 4 goals for the Italy national football team between 1967 and 1972, making his debut on 1 November 1967, in a 5–0 home win over Cyprus in a UEFA Euro 1968 qualifying match. He later played in the European championship-winning team at Euro 1968 on home soil, appearing in the 2–0 final replay victory over Yugoslavia in Rome, at the age of 25. He was also a member of the Italian side that finished runners-up at the 1970 FIFA World Cup in Mexico.