Pioli, a native of Parma, started his own playing career for his home city team, AC 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 1998 for Fiorenzuola of Serie C1, after two experiences with Padova and Pistoiese.
From 1999 to 2002 Pioli coached Bologna's youth team (winning a championship with Allievi Nazionali's team), and Chievo Verona's in 2002-2003. In 2003-2004, 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 February 12, 2007 after a 3-0 loss to AS Roma which brought Parma down to second-last place and replaced by Claudio Ranieri. On September 11, 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.
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.