Pioli, a native of Parma, started his own playing career for his home city team, Parma. Successively, he was signed by Juventus, with whom he had his Serie A debut in 1984. Sold to Verona in 1987, Pioli moved to Fiorentina in 1989, where he spent six years of his career. He ended his career in 1999 for Colorno of Eccellenza Emilia-Romagna (Italian 6th highest level at that time; top level of Emilia-Romagna regional league system), after three experiences with Padova, Pistoiese and Fiorenzuola. He concluded his career playing in Colorno on the team with his brother Leonardo.
From 1999 to 2002 Pioli coached Bologna's youth team (winning a championship with Allievi Nazionali's team), and Chievo's in 2002–03. In 2003–04, he was appointed as head coach of Serie B club Salernitana. He moved to Modena, still of Serie B, in 2004.
In 2006, Pioli was named as Parma's head coach, therefore returning to his home city and marking his Serie A debut as a manager. He was however sacked on 12 February 2007 after a 3–0 loss to Roma which brought Parma down to second-last place and replaced by Claudio Ranieri.
On 11 September 2007, he was unveiled as new head coach of Serie B club Grosseto, replacing Giorgio Roselli, sacked after three consecutive defeats in the first three league matches, and managed to lead the Tuscan minnows to an impressive mid-table finish in their first season in the Serie B. He then served as head coach of Piacenza for their 2008–09 Serie B campaign. In July 2009 he left Piacenza to join Sassuolo as new head coach of the neroverdi.
On 10 June 2010, Pioli was named as head coach of Serie A club Chievo on a twelve-month contract.
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.
On 4 October 2011 he was named new head coach of Bologna in Serie A, in place of the sacked Pierpaolo Bisoli. 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.
On 12 June 2014, it was confirmed Pioli's appointment as new head coach of Lazio in place of Edoardo Reja. In his first season at the club, he led Lazio to a third-place Serie A finish. On 11 June 2015 he was offered a new 2+1-year contract.
On 3 April 2016, he was sacked after a 4–1 home defeat to city rivals Roma.
On 8 November 2016, Pioli was appointed as the new head coach of Internazionale on an eighteen-month contract. On 20 November, Inter drew 2-2 against AC Milan in a Serie A Derby della Madonnina match, Pioli's first competitive match as head coach of the club. He was sacked on 9 May 2017. Inter had won 12 of the first 16 Serie A matches that Pioli was in charge of (draw with AC Milan, losses to Napoli, Juventus and Roma) but this was followed by 2 draws and 5 losses in their last 7 Serie A matches prior to his sacking.
On 6 June 2017, Pioli was named new head coach of Fiorentina. He signed for two years with another optional year.As of 16 September 2017
Serie C1: 1983–84
Serie A: 1985–86
European Cup: 1984–85
European Super Cup: 1984
Intercontinental Cup: 1985
Serie B: 1993–94
Allievi Under-17 National Championship: 2000–01