He won 17 major titles with Milan, including five Serie A championships and three UEFA Champions League tournaments, reaching five finals in total.

He is mostly remembered for his role alongside Paolo Maldini, Franco Baresi, Alessandro Costacurta, Filippo Galli and Christian Panucci in the Milan backline under managers Arrigo Sacchi and Fabio Capello, forming what is considered by many in the sport to be one of the greatest defensive lineups of all time.

[a] An Italian international in the early 1990s, Tassotti only came into the national side under Sacchi, when he was already in his 30s, helping Italy to qualify for the 1994 FIFA World Cup.

Although this was a fairly bleak period in the club's history, as they failed to dominate in the league or capture a trophy, the squad did reach the Coppa Italia final during the 1984–85 season, and were able to regularly qualify for the European competitions, frequently finishing in the top half of the table.

[14] Tassotti became a central figure in the Milan squad of the late 1980s and early 1990s under Arrigo Sacchi, and subsequently Fabio Capello, usually wearing the number 2 shirt.

[11] Tassotti did not win his first cap for Italy until age 32, under Arrigo Sacchi, in a 2–2 home draw against Switzerland in a 1994 FIFA World Cup qualifier on 14 October 1992.

[14] This was partly because of an abundance of other world class Italian defenders, as he was constantly overlooked by Sacchi's predecessor Azeglio Vicini, who preferred to deploy full backs he had worked with during his tenure as Italy's under-21 coach, despite Tassotti's excellent club performances.

However, in the quarter-final match, Tassotti elbowed Spanish midfielder Luis Enrique in the face during stoppage time in the second half, breaking the Spaniard's nose.

[24][25][26] In the 2001–02 season, Tassotti joined Milan's coaching staff under former teammate Carlo Ancelotti as an assistant manager, and retained his post after the latter's departure, under Leonardo, Massimiliano Allegri, Clarence Seedorf and Filippo Inzaghi.

[23][27][28] In January 2014, he acted as caretaker manager for one match, a 3–1 home win over Spezia for the campaign's Coppa Italia following Massimiliano Allegri's dismissal and before Clarence Seedorf's appointment.

[11][12][13][14][23][32] Although Tassotti primarily excelled defensively, he was a modern and versatile full back who was also one of the first players in his position to be capable of being an offensive threat, due to his pace, athleticism, stamina, technique, control, and distribution, as well as his ability to make overlapping attacking runs, dribble, and provide accurate crosses and assists from the right wing.

[14][23][32][38][39][40] Although he was initially not known for being particularly skilful, Tassotti was later also highly regarded for his elegance on the ball and technical ability, which he was able to improve extensively under the tutelage of manager Nils Liedholm while at Milan.