He most notably led AC Milan to the Serie A title in the 2021–22 season, a club's scudetto last accomplished over a decade earlier.

[3] An elegant, tenacious, physical, and mobile defender, Pioli was capable of playing anywhere along the back-line, although he performed best as a man-marking centre-back, or "stopper," in Italian.

However, he was sacked on 12 February 2007[citation needed] after a 3–0 loss to Roma which brought Parma down to second-last place and replaced by Claudio Ranieri.

[9] On 2 June 2011, Pioli was named head coach of Serie A club Palermo, but he was relieved of his duties just 90 days later.

[11] After two troublesome seasons with Bologna, both ended with the team struggling in the bottom half of the Serie A table but always escaping relegation, he was removed from his managerial duties on 8 January 2014, with Davide Ballardini appointed as his replacement.

[19] The day after Marco Giampaolo's sacking,[20] on 9 October 2019, Pioli was appointed as the new coach of AC Milan, on a deal to the end of the season.

[24] On 21 July, Pioli reached an agreement with Milan for a two-year deal extension of his contract as head coach to June 2022.

[26] On 6 December Milan beat Sampdoria 2–1, setting a new club record for goals scored in successive Serie A matches (30).

[28] On 23 December, Milan beat Lazio 3–2, becoming the second side in the history of Europe's top five leagues to have scored two or more goals in more than 15 successive games in a single calendar year (after Barcelona, 18 in 1948).

[30] Three days later, Pioli's side beat Torino 7–0 in an away game, winning by a seven-goal margin, last accomplished against Udinese (7–0) in June 1959.

Milan also set a new all-time record for away wins in a Serie A season with 16; no side has ever done better in Europe’s top five leagues in a single campaign.

[38] In December, his Milan side became the second team in Serie A history to win at least 17 away league games in a single calendar year (after Napoli, 18 in 2017).

[47] Pioli's tenure at Milan has brought him the praise of several Italian football personalities and pundits, such as Alberto Zaccheroni, Fabio Capello, Claudio Ranieri, Arrigo Sacchi and Adriano Galliani.

[65] On 18 September 2024, Al Nassr announced that Pioli had signed a deal to coach the team after they dismissed Luís Castro.

Due to his passion for basketball, he attempted to bring strategic elements of the sport into his own tactical approach as a football manager.

Another key feature of this formation was in the center, where two pairs of holding and attacking midfielders formed a square, supporting each other offensively and defensively.

[72] However, with the arrival of Zlatan Ibrahimović in January 2020, Pioli switched Milan's formation to his long favored 4–2–3–1, primarily in order to accommodate for the Swedish ageing yet prolific goalscorer, in which he would play up front without much of a defensive work other than pressing, alternating between the roles of a classical striker, a target forward, and a false 9.

[74][75] Ante Rebić and Ismaël Bennacer, the two high-profile new arrivals struggling to fit into the previous coach's system, were given a few more opportunities to prove themselves; as a result, the former got to play in his favorite position as a left winger and quickly topped the club's seasonal goalscoring chart, while the latter formed an efficient double pivot with Franck Kessié, who also significantly improved the quality of his performances.

[76][77][78] During the 2022–23 season at AC Milan, Pioli switched from 4–2–3–1 to 3–4–2–1 formation, forming a back-three of Pierre Kalulu, Fikayo Tomori, and Malick Thiaw, which helped the team play with a high defense line.

[80][81] Through his management career, Pioli has built a reputation as a coach who works well with young players, is a good motivator and who displays tactical flexibility.

[83] While in quarantine, Pioli continued to be in charge of the team via Zoom and with the help of another member of his coaching staff, Daniele Bonera.