On March 28, 2015 De Biasi obtained Albanian citizenship.
De Biasi, a midfielder, started his professional playing career for Inter Milan; he was part of the first team squad but, despite this, never played for the nerazzurri and was then loaned to Serie C team Reggiana in 1975 and newly promoted Serie A club Pescara Calcio one year later. He was sold to Brescia in 1977 as partial compensation for the signing of Evaristo Beccalossi by Inter. De Biasi played in Brescia for five seasons, only one of them in Serie A. He then moved to Palermo in 1983, but abruptly left it three years later following the cancellation of the Sicilian club in the summer of 1986. This was followed by a single season with Vicenza and two Serie C2 seasons for Treviso. De Biasi retired from active football in 1990, after a Serie D season with Bassano.
In 1990, De Biasi became youth team coach for Bassano; in 1991, he was appointed by Vicenza to coach the allievi nazionali youth squad. In 1992, De Biasi made his debut as first team coach, being boss of Serie C2 club Vastese (now Pro Vasto); this was followed by three seasons as Carpi boss. In 1996, De Biasi was appointed coach of Serie B club Cosenza, but was fired on Christmas' eve day. After a two-year spell at SPAL, De Biasi was contacted and hired by Serie C1 club Modena on 2000; with the canarini, De Biasi obtained two consecutive promotions that brought Modena back in Serie A after 38 years. He left Modena in 2003, after having led his club to a good 13th place in the Serie A table, and signed for Brescia, where he had the opportunity to coach Roberto Baggio in his last playing season of his career. He was sacked during the 2004–05 season.
In 2005, Torino of Serie B appointed De Biasi as head coach, offering him a squad quickly built in a very few days following the cancellation of the old Torino Calcio club and the forming of a new society, owned by Urbano Cairo. Under De Biasi, Torino obtained immediate Serie A promotion, after having defeated Mantova on play-offs. De Biasi, initially confirmed as head coach also for the 2006–07 Serie A campaign, was however sacked three days before the first matchday and replaced by Alberto Zaccheroni. On 26 February 2007 Torino FC chairman Cairo decided to sack Zaccheroni too and recall De Biasi at the helm of the granata, leading them to avoid relegation.
After several rumours regarding a possible move to La Liga side Levante UD, he was announced on 9 October 2007 to have reached an agreement with the Spanish side, where he will join fellow Italians Damiano Tommasi, Christian Riganò, Marco Storari and Bruno Cirillo. He did not manage to save the club from relegation, mainly because of financial struggles which questioned the club's own survival and led to sell several key players during the January transfer window. Despite the lack of top-quality players and as the risk of bankruptcy loomed, he led the team to some unexpected victories, displaying linearity and tactical discipline that gained him the love of the Spanish fans and esteem of the critics: in one of its editions, the popular sports daily “As” declared him the best coach in the championship
On 16 April 2008 he was announced by Torino to replace Walter Novellino for the five final matchdays, with the aim to save the club from relegation once again. Once again, De Biasi saved the team. On 8 December 2008 he was sacked after fifteen matches, blamed by the team's manager for the fact that Torino was once again struggling to avoid relegation. However, despite hiring and then dismissing a second and then a third coach, the team was still relegated at the end of the championship.
On 22 December 2009 Udinese dismissed manager Pasquale Marino and appointed De Biasi to take charge of the struggling team from North-Eastern Italy. However, results did not particularly improve under his tenure as head coach, and De Biasi himself was removed from his post on 21 February 2010 with Marino being named back at the helm of the club.
On 14 December 2011, following Josip Kuže's dismissal, the Albanian Football Association announced to have agreed a two-year deal with De Biasi as new head coach of the national team for the 2014 FIFA World Cup qualifiers. His first match as Albania manager was a 2–1 defeat to Georgia, during which Edgar Çani, one of his innovations, scored after three minutes for the Red and Blacks.
In May 2012, in two friendlies against Qatar and Iran, De Biasi launched new players such as Mërgim Mavraj, Mërgim Brahimi, and Etrit Berisha, whereas in the friendly against Moldova, scheduled on 16 August 2012, he convocated three young players, Erjon Dushku, Erjon Vuçaj, and Renato Arapi. Albania won narrowly against Iran and Qatar, but was held by Moldova at home.
De Biasi won his first competitive match on 7 September 2012, defeating Cyprus 2–0 in their opening 2014 World Cup Qualifying match, in Tirana, with goals by Sadiku, Çani and Bogdani. This match saw two newcomers to the Albania's midfield, Alban Meha and Burim Kukeli, who played for the entire match. On 22 March 2013, he led Albania with his schemes and defensive tactical to a 1–0 historic win against Norway at Oslo, moving Albania into joint 2nd place in the group 9 points, ahead of Norway who were left on 7 points.
De Biasi started UEFA Euro 2016 qualifier with a 1–0 win over group favorites Portugal. This victory was described as historic by Albanian and international medias, and caused the resignation of Portugal's coach, Paulo Bento. In the next qualifying match against Denmark at the newly renovated Elbasan Arena, Albania was on lead until 81st minute when Lasse Vibe levelled the score to 1–1. The Albanian goal was scored by Ermir Lenjani, another player brought by De Biasi in 2013.
On 29 March 2015, in the fourth qualifying match against Armenia, Albania was behind after only four minutes, but with the clever substitutes of De Biasi, Albania come back and won the match 2–1 thanks to goals from Mërgim Mavraj and Shkëlzen Gashi, a player who came on in the 46th minute. This match caused the resignation of Armenia's coach, Bernard Challandes.
On 13 June 2015, Albania beat one-time World Champions France at Elbasan Arena for the first time in history thanks to a free-kick from Ergys Kaçe in the 43rd minute. For this match, De Biasi left some of the starter players out, in order to rest. The victory subsequently allowed Albania to climb 15 positions to 36th place in the July 2015 FIFA world rankings for the first time in history.
Gianni De Biasi became the first coach of the Albanian national side to lead the team to qualify for the UEFA European Championship, when the team sealed qualification for UEFA Euro 2016 on 10 October 2015. For this achievement De Biasi, as well as the entire team were bestowed the Honor of Nation Order by Albania's President Bujar Nishani.
At the end of 2015, De Biasi was included for the first time in the top ten IFFHS National Coaches of the World, ranking sixth. On 9 January 2016, he agreed a contract extension with Albania, signing until 2017, also his new salary was increased by 60% of his former salary. On 7 March 2016, he was awarded by FIGC with the "Special Golden Bench" award for "spreading the values of the Italian school coaches in the world".
In UEFA Euro 2016, Albania was pitted against France, Switzerland and Romania in Group A. After losing narrowly to Switzerland in their opening game, Albania held hosts and favourites France scoreless until the 89th minute before conceding two late goals. In their final group game, a 43rd minute headed goal by Sadiku was the only goal in a 1–0 win and gave them a historic first victory in the European Championships, helping them to a 3rd-place finish in the group.
Following the eliminaton of Albania from UEFA Euro 2016, De Biasi confirmed himself that he would stay at Albania for the qualifiers of the 2018 FIFA World Cup.
On 14 June 2017, De Biasi announced his resignation in a joint press conference with the President of the Albanian Football Federation.
On 22 September 2017, De Biasi was appointed manager of Spanish club Deportivo Alavés.As of 22 September 2017