He made his senior international debut at UEFA Euro 1968 on home soil, and is widely known for later scoring in the final victory over Yugoslavia, which gave Italy their first ever European Championship title.

He made his professional debut with Missiminiana di Catania in Serie D, showing promising goalscoring prowess during the 1965–66 season, in which he scored 18 goals.

[1] In 1976, Anastasi began to find less space within the first team Juventus squad, partially due to his disagreements with manager Carlo Parola, and he transferred to Inter in exchange for Roberto Boninsegna.

[8] With the Italy national team, Anastasi was a member of the squad that won the 1968 UEFA European Football Championship on home soil,[9] a tournament during which he made his international debut during the first leg of the final against Yugoslavia at the Stadio Olimpico in Rome on 8 June, which ended in a 1–1 draw.

In his place, and that of midfielder Giovanni Lodetti, two strikers were called up by manager Ferruccio Valcareggi: Roberto Boninsegna and Pierino Prati, as Italy went on to reach the final.

[13] Anastasi also participated at the 1974 FIFA World Cup, scoring one goal in the team's 3–1 victory against Haiti in the first round, although Italy failed to advance from their group.

[8][15] Anastasi is regarded as one of the best Italian strikers of his generation,[1] as he was a fast, physical, hard-working, reliable, and agile forward, with good reactions.

[1][2][16][17] A diminutive player with a sturdy build, Anastasi usually played as a striker in the centre-forward position, like his idol, John Charles; however, he had a rather modern and unorthodox interpretation of this role, and did not function as a traditional number nine, who mainly operated inside the box.

[1][2][3][16][17][18][19][20][21][22][23][24] Despite not having the best first touch, or being the most naturally creative, tactical, or skilful player, he was a talented player and a fast sprinter, who possessed excellent acceleration and anticipation, as well as good dribbling skills with either foot, which led the Italian journalist Cesare Lanza to compare him to Luigi Meroni; as such, he also played on the right wing on occasion, due to his flair, solid technique, and crossing ability, and he even had a tendency to drift onto the left flank when he was deployed as an out-and-out striker in order to create chances for his teammates.

[2][29] In addition to his playing ability, as a Sicilian who had success Juventus, Anastasi – as well as several of his other southern–Italian club teammates – also became a social symbol for many other southern Italian immigrants in a time of great social divide between the northern and the southern regions of the country; in particular, he became an icon for factory-workers who had moved from the South of Italy to Turin in order to find work with Fiat.

[18][28] His other nicknames were "Petruzzo" and "Petru 'u turcu" ("Peter the Turk", in the Sicilian dialect), due to the dark, olive-colour of his complexion whenever he was tanned.