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, most notably winning the Serie B top-scorer Award during the 1988–89 Serie B season, with 23 goals. He then joined Turin club Juventus, and made his debut 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, under manager Giovanni Trapattoni; Schillaci’s arrival coincided with a return to form under the direction of former legendary Juventus goalkeeper Dino Zoff. He featured prominently for the Turinese club that season, scoring 15 league goals and 21 in all competitions in a very positive year, which ended with Juventus winning both the 1989–90 Coppa Italia and the UEFA Cup titles. Due to his clever, inventive, and aggressive attacking 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 making one over-age appearance for the Italy Under-21 side, under Cesare Maldini, Schillaci made his senior international debut for Italy under manager Azeglio Vicini, on 31 March 1990, in a 1–0 friendly away win over Switzerland, in Basel. He was subsequently called up for Italy’s squad for the 1990 World Cup, to be played on home soil.

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 started alongside Baggio in Italy’s next two matches of the knock-out stages, also opening the scoring in the round of 16 and quarter-finals, against Uruguay and the Republic of Ireland respectively, and set up Aldo Serena’s goal against Uruguay.

After setting up Baggio’s opening goal, 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, as well as the Golden Ball Award for the best player of the tournament. Overall, he scored seven goals in sixteen caps for Italy between 1990 and 1991, scoring his only other goal for Italy in a 2–1 defeat away against Norway, in 1991, in an UEFA Euro 1992 qualifying match.

After the end of the 1990 World Cup, Schillaci played one more year for Juventus, alongside his Italy attacking team-mate Roberto Baggio, before joining Internazionale. Schillaci ultimately fell short of the expectations of the Inter fans, as well as those of Juventus, mainly because of the physical troubles which he suffered after the 1990 campaign. In 1994, he joined Japanese club Júbilo Iwata, becoming the first Italian player to play in the J. League, and he won the J. League Division 1 title with the club in 1997. He retired in 1999.

Schillaci retired in 1999. Today he lives back in his native Palermo, where he owns a youth academy of football.