Malesani career as player was mostly spent on a Veronese amateur team Audace S. Michele, where he obtained a promotion from Serie D to Serie C in 1976–77, appearing fourteen times on that season. He retired from playing football at the age of 24, and worked at Canon in Amsterdam, where he studied the Ajax Amsterdamtotal football training methods. His passion for coaching was so great, that on his honeymoon, he decided to go toBarcelona in order to watch Johan Cruijff's coaching sessions at Barcelona FC. Malesani left his job at Canon in 1990 order to pursue a coaching career at Serie C1 team Chievo for the Allievi youth squad. In 1991, he is assistant of head coachCarlo De Angelis in the first team, and in 1993 he becomes head coach himself. His first season as head coach ended in a historical promotion to Serie B for then-unknown Chievo.
Malesani left Chievo in 1997, after three impressive Serie B seasons and a narrowly missed promotion in the Serie A league in order to become Fiorentina's boss, in what was his first stint in the Italian top flight. A good Fiorentina season convinced Parma to appoint Malesani as new head coach in 1998, where he won a Coppa Italia, a UEFA Cup, an Italian Super Cup and obtained two fourth places before being sacked during the 2000–01 season.
After losing his job at Parma, Malesani then coached Verona and Modena, failing to save the clubs from relegation in both cases; successively he moved abroad to coach Greek side Panathinaikos. Panathinaikos remains the club with the highest percentage of wins in Malesani's career to date. Malesani was appointed coach of Udinese in January 2007, as replacement for Giovanni Galeone. He led his side to a not particularly impressive tenth place in the 2006–07 Serie Afinal table, only seven points far from relegation, being not confirmed for the following season. On 27 November 2007 he was unveiled as Empoli's new head coach, replacing Luigi Cagni. He was axed on 31 March 2008 following a 2–0 home defeat to U.C. Sampdoria which left Empoli down in last place in the league table.
On 23 November 2009, he was appointed as the new head coach of Siena, replacing Marco Baroni. On 21 May 2010, was released by Siena. On 1 September 2010, he signed a one-year contract for Bologna. After a successful season which saw his club finish in 16th place, six points clear of relegation, despite a three-point deduction for tax problems and running feuds over the club's ownership, Malesani was replaced by Pierpaolo Bisoli on 26 May 2011.
On 19 June 2011, Genoa officially announced that Malesani would be the new first team head coach. However, after Genoa was defeated 6-1 by Napoli, Malesani was fired. He returned to Genoa on 2 April 2012, taking over from Pasquale Marino who had previously replaced him only to be sacked a few months later. His second stint as Genoa boss lasted however only twenty days, as he was sacked once again on 22 April after a 1–4 home loss to Siena that left Genoa one point shy of relegation, and led to massive protests from Genoa fans during the game.
On 5 February 2013, Malesani was appointed as the manager of Palermo. However, after three matches in charge, on 24 February 2013 Malesani was relieved from his duties as the manager.
