Born in Palermo, Italy, from a poor family, Schillaci started to play for an amateur team of his native city, Amat Palermo. He then signed in 1982 for the Sicilian club Messina, where he played until 1989 and showed his goal-scoring abilities. He then joined Juventus of Turin, and debuted in Serie A on 27 August 1989. Juventus, the "Old Lady" of Italian football, was at the time suffering from the breakup of the wonder team which dominated Italian football in the 1980s and Schillaci's arrival coincided with a return to form under the direction of former goalkeeper Dino Zoff. He featured prominently, scoring 15 goals, in a very positive year for the Turinese club which ended the season winning both the Coppa Italia and the UEFA Cup. Due to his inventive, aggressive attack style he was then selected by head coach of Italy, Azeglio Vicini, to play in the 1990 FIFA World Cup, to be hosted by Italy itself, despite being a novice in the arena of national team competitions.
After the end of the 1990 World Cup, Schillaci played one more year for Juventus, before joining Internazionale. Schillaci did not leave a great record for the Inter fans, as well as for the Juventus ones, mainly because of physical troubles which he suffered after the 1990 campaign. In 1994 he joined Japanese club Jubilo Iwata, becoming the first Italian player to play in the J. League.
Schillaci retired in 1999. Today he lives back in his native Palermo, where he owns a youth academy of football.
At the 1990 World Cup, Schillaci replaced Andrea Carnevale during Italy's first match against Austria. He scored the decisive goal as the match ended with a 1–0 win for Italy. Against the USA, Schillaci again made an appearance as a substitute, but he started the next match, against Czechoslovakia, alongside Roberto Baggio. Italy won 2–0, with Baggio and Schillaci both scoring. Schillaci also opened the scoring in Italy's matches in the second round and quarter-finals, against Uruguay and the Republic of Ireland respectively.
For the semi-final against Argentina, Gianluca Vialli replaced Baggio, whereas Schillaci kept his place in the team. The match ended 1–1, with Schillaci scoring his fifth goal of the tournament, but Italy were eliminated after a penalty shoot-out.
Schillaci scored the winning goal in Italy's 2–1 win in the third-place match against England from a penalty, and won the Golden Boot, with six goals. He retired from international competition with seven goals in sixteen caps after scoring his only other goal for Italy against Norway in 1991.