In June 2002, he was signed by Roma in a co-ownership deal, for €3.1 million, (who also saw Marco Amelia, move in the opposite direction, for €2.8 million) however, he was loaned back to Livorno for the 2002–03 Serie B season, after they had earned promotion. In his first Serie B season, Chiellini made six seasonal appearances, also making his Coppa Italia debut. In his second Serie B season, Chiellini broke into the starting line-up for the club, and would go on to make 42 official appearances, also scoring four goals from his left back position.

Chiellini represented Italy at all youth levels, and he won the European Under-19 Championship with Italy in 2003, and was also a member of the Italy team that won the bronze medal at the football tournament of the 2004 Summer Olympics. He participated in the 2006 and 2007 U-21 Championships as Italy’s captain, scoring 2 goals over both tournaments, although Italy were eliminated in the group stage on both occasions. He was named in the ‘UEFA Team of the tournament’ of the 2007 U-21 Championships held in the Netherlands, where Italy also obtained qualification for the 2008 Summer Olympics. In total, he made 26 appearances for the Under-21 side, scoring 6 goals.

In June 2004, Livorno officially bought back Chiellini for €3 million. During his four-season spell with the clubs’ first team, Chiellini made a total of 57 appearances, scoring four goals, before his transfer to Juventus.

He made his debut for the Italian national team on 17 November 2004 against Finland under Marcello Lippi, at the age of 20. He became a regular squad member since 2007 and he scored his first goal for Italy on 21 November 2007, against the Faroe Islands, in Modena, in a UEFA Euro 2008 qualifying match.

With Juventus back in Serie A for the 2007–08 season, Chiellini again was a starter for the club at left back, but following injuries to Jorge Andrade and Domenico Criscito, he was shifted to centre back again. Chiellini had a tremendous season and eventually made the position his own. Alongside fellow centre-half Nicola Legrottaglie, the duo were instrumental as Juventus finished the season with the joint second-best defensive record. The surprising aspect of this is that neither were considered remotely close to pinning down a centre back position in the summer before the season, with Domenico Criscito and Jorge Andrade preferred as the starting duo. He has been a regular fixture in the Juventus backline since their return to Serie A and was notably named Man of the Match in a game against Juventus rivals, Internazionale when he won a physical and heated duel with former teammate Zlatan Ibrahimović, keeping the Swedish striker at bay. Chiellini extended his original contract from until 2009 to 2011 on 12 October 2006. On 27 April 2008, Chiellini scored twice for Juventus in 5–2 win over Lazio that confirmed Juventus’s place in the Serie A top four. on 26 June 2008, Chiellini extended his contract with Juventus until 2013.

During the 2008–09 season, Chiellini remained as first choice in central defence alongside Nicola Legrottaglie. Chiellini scored his first goal in Europe on 13 August 2008 as Juve beat Artmedia Petržalka 4–0 in the first leg of the UEFA Champions League third qualifying round tie. Four days later, he injured his left knee again during the Trofeo Luigi Berlusconi against Milan and missed the start of the Serie A season, returning to duty in September starting in each of Juve’s first three Champions League group games. At the end of the year, he was named Serie A Defender of the Year for 2008 at the annual Oscar del Calcio awards ceremony. On 10 March 2009, Chiellini was sent off for a second bookable offense during the Champions League first knockout round second leg tie at home in a tightly contested match against Chelsea, but Juventus were eliminated 3–2 on aggregate after holding the former English champions to a 2–2 draw.

An injury sustained in the win over Fiorentina on 6 March 2010 sidelined him for several important games and, in his absence, Juventus embarked on a miserable run of form, conceding nine goals in the four games he missed. He marked his return by scoring the opening goal away at Napoli but was unable to prevent Juventus from succumbing to a 3–1 defeat. On 23 November 2010, Chiellini extended his contract with Juventus again until 30 June 2015 and was given a pay raise.

During 2010 World Cup qualifying, Chiellini cemented his place as an undisputed first-choice in Marcello Lippi’s squad. He played the full 90 minutes in all three group matches at the 2009 FIFA Confederations Cup but Italy were eliminated at the group stages on goal difference. He was also the starting Italy centre back, along with Cannavaro, in the 2010 World Cup, although Italy disappointed and exited in the first round, finishing in last place in their group with two points, and failing to win a match or keep a clean sheet.

Chiellini was raised in Livorno and is one of twin boys. He completed a laurea (bachelor’s degree) in economics and commerce at the University of Turin in July 2010, and earned a laurea magistrale (master’s degree) in business administration in April 2017 from the same institution, graduating cum laude (with honours). Chiellini is able to speak English.

Under manager Antonio Conte, Chiellini returned to his original position at left back due to Barzagli and Bonucci’s good run of form. After struggling to re-adapt back to his former position, he grew into his role and managed to keep Paolo De Ceglie, the only other natural left back in the squad, on the bench for much of the first half of the 2011–12 season. In the second half of the 2011–12 season, Conte switched to a three-man defence, where Chiellini partnered Bonucci and Barzagli in a very successful defensive system for Juve, who ended the season as Serie A champions, with the best defensive record, as well as being unbeaten in the league. Due to their performances together, the three-man defence earned the nickname BBC, a reference to the players’ initials, and soon the trio established themselves as one of the best defences in world football during the following seasons. Juventus lost the 2012 Coppa Italia Final against Napoli, but would later defeat them in the 2012 Supercoppa Italiana, although Chiellini would miss the match.

Chiellini made his 250th appearance with Juventus on 22 September 2012, on his first appearance of the 2012–13 season after coming back from injury, in a 2–0 home win over Chievo. On 1 March 2013, after coming back from another injury suffered in mid-December, he scored a header in a 1–1 draw over Napoli at the San Paolo stadium, which allowed Juventus to keep their 6-point lead over Napoli, who were in second place. Juventus retained the Serie A title and the Supercoppa Italiana that season, once again finishing the year with the best defensive record in Italy. Chiellini was the only Italian player to be nominated for the 2013 UEFA Team of the Year.

On 14 November 2012, in a 2–1 friendly defeat to France, Chiellini wore the captain’s armband with Italy for the first time in his career.

On 6 October 2013, Chiellini scored in Juventus’s 3–2 win over Milan, scoring the match winning goal; the next day he announced the renewal of his contract with Juventus, which would keep him at the club until 2017. He made his 300th appearance with Juventus in a 3–0 Serie A victory against Roma on 5 January 2014, as he went on to win his third consecutive league title with Juventus that season.

On 22 June 2013, Chiellini scored his third goal for Italy against Brazil in the 2013 Confederations Cup in a 2–4 defeat, a low shot to the net after the referee Ravshan Irmatov had initially signaled for a penalty kick to Italy. Italy managed to finish the tournament in third place, following a 3–2 penalty shootout win over Uruguay in the bronze medal match.

In the 2014 Supercoppa Italiana on 22 December 2014, Juventus were defeated by Napoli on penalties after a 2–2 draw following extra-time; Chiellini missed one of Juventus’s spot-kicks in the resulting shoot-out. On 20 May, Chiellini captained Juventus in the club’s 2–1 win over Lazio in the 2015 Coppa Italia Final, also scoring Juventus’s first goal of the night.

In the 2014 FIFA World Cup Qualifying fixture against the Czech Republic, at the Juventus Stadium in Turin, on 10 September 2013, Chiellini scored Italy’s first goal in a 2–1 home win, which allowed the nation to clinch the top spot in their group and qualify for the 2014 FIFA World Cup in Brazil with two games at hand; this was the first time that the Italian squad had done so.

During the 2014 World Cup, in Italy’s final group stage game against Uruguay, replays showed Luis Suárez biting Chiellini on the shoulder before Suárez fell and clutched his face, in Suárez’s third career biting incident. As the Italian players protested to the Mexican referee Marco Antonio Rodríguez for not penalizing Suárez, Uruguay won a corner and scored, winning 1–0 to qualify for the last 16 and eliminating Italy. As a result, the FIFA Disciplinary Committee launched an investigation into the incident. On 26 June, The FIFA Disciplinary Committee announced that Suárez would be suspended for nine matches and banned from any football activity (including entering any stadium) for four months. Suárez was also fined CHF100,000 (approx. £65,700/€82,000/US$119,000). Even so, Chiellini expressed his view that the four-month ban for Suárez was “excessive”.

On 10 October 2014 in a UEFA Euro 2016 qualifying match against Azerbaijan in Palermo, Chiellini put Italy ahead with a first-half header. He then scored a late own goal, but headed a winner three minutes from time to give Italy a 2–1 victory. Italy qualified for Euro 2016 on 10 October of the following year after a 3–1 win over Azerbaijan. On 17 November 2015, Chiellini made his 82nd appearance for Italy in a 2–2 friendly home draw against Romania, overtaking Franco Baresi, Giuseppe Bergomi, and Marco Tardelli as Italy’s tenth most capped player of all time. On 31 May 2016, Chiellini was named to Conte’s 23-man Italy squad for Euro 2016. Playing alongside Bonucci and Barzagli, Chiellini drew praise for his defensive performances, as he helped Italy keep clean-sheets in both of their opening two victories over Belgium and Sweden, which enabled the nation to top their group and advance to the second round. Having been booked for a tactical foul in Italy’s opening match on 13 June, Chiellini was rested for Italy’s final group match against Ireland on 22 June, which ended in a 1–0 defeat. In the round of 16 at Stade de France in Paris on 27 June, he scored the opening goal in a 2–0 win over reigning European champions Spain and helped Italy record their third clean-sheet of the tournament. Italy were eliminated from the competition in a 6–5 penalty shoot-out defeat to reigning World Cup champions Germany in the quarter-finals, on 2 July.

In July 2014, Chiellini married his long-time girlfriend Carolina Bonistalli at a private Catholic ceremony at the Sanctuary of Montenero in Livorno. The couple have two daughters: Nina born July 2015, and Olivia born June 2019. That same year, he published a book, C’è un angelo bianconero. Il mio maestro si chiama Scirea.

On 4 June 2015, it was confirmed that Chiellini would not participate in the 2015 UEFA Champions League Final against Barcelona as a scan on his left leg revealed he had a first degree calf muscle tear. In the absence of Chiellini, Juventus were defeated 3–1 by Barcelona at Berlin’s Olympiastadion.

On 28 April, he made his 300th appearance in Serie A with Juventus in a 2–2 away draw against Atalanta. On 3 June, after Chiellini missed out on the 2015 Champions League Final, he started in the 2017 final, Juventus’ second final appearance in three years, but were defeated 4–1 by defending champions Real Madrid.

On 9 February 2016, it was confirmed that Chiellini would miss the Serie A match on 13 February against Napoli, as well as the first round of 16 leg of the Champions League on 23 February against Bayern Munich due to an injury. Chiellini returned to action on 28 February to take on rivals Internazionale, yet again sustaining an injury to his thigh which caused him to limp off the pitch and substituted off in the 35th minute. After already having missed the first round of 16 leg against Bayern, there was further doubt as to if he would miss the second leg as well on 16 March. However, after medical testing it was estimated he would only be out for ten days, initially thought to only miss the second leg of the Coppa Italia semi-finals against Internazionale on 2 March and a Serie A match against Atalanta on 6 March; he wouldn’t be fit for the second round of 16 leg of the Champions League, and missed the match. He returned from injury on 2 April, starting in a 1–0 home win over Empoli, but sustained yet another injury to his adductor longus muscle in his right thigh before being substituted off in the 54th minute of that match; further tests in the following days revealed he would be out for 20 days. He returned to action once again in a 2–1 away defeat to Verona, on 8 May. After constant injury spells throughout the season, Chiellini scored in the last match of the season on 14 May in the 77th minute of a 5–0 home win over Sampdoria, as Juventus celebrated winning the league title for a fifth consecutive time since the 2011–12 season; this was Chiellini’s 400th appearance for Juventus. On 21 May, Chiellini captained Juventus in the 2016 Coppa Italia Final in Rome; he played a key role in a 1–0 extra-time victory over Milan (the club’s eleventh Coppa Italia title in total), helping his team to defend the title and keep a clean sheet. He later lifted the trophy as Juventus became the first Italian club ever to win consecutive domestic doubles.

On 26 October 2016, Chiellini scored two goals in a 4–1 home win over Sampdoria after three weeks out due to injury. On 23 December, Chiellini scored the opening goal in the Supercoppa Italiana against Milan, but it ended in defeat as Milan won 4–3 in penalty shoot-out following a 1–1 draw after extra time.

In Italy’s opening 2018 FIFA World Cup qualification match against Israel on 5 September 2016, Chiellini earned his 90th international cap, but was later given his first ever national team red card after a second bookable offense in the 55th minute of an eventual 3–1 away win; causing him to miss the next group match against Spain on 6 October, an eventual 1–1 draw.

On 12 September 2017, Chiellini missed the opening 2017–18 Champions League group stage match of the season against Barcelona, due to a calf injury.

Chiellini also missed the return match against Spain on 2 September 2017, an eventual 3–0 away loss, as well as the return march against Israel on 5 September, an eventual 1–0 home win, with a calf injury. On 9 October, Chiellini made his 94th appearance for Italy in a 1–0 away victory over Albania in a World Cup qualifier, equalling Giacinto Facchetti as the nation’s joint-eighth highest appearance holder of all time. Italy finished in Group G in second place behind Spain, and advanced to the play-off against Sweden. Italy failed to qualify for the 2018 FIFA World Cup after a 1–0 aggregate loss to Sweden. Immediately following the second leg – a 0–0 home draw on 13 November –, was initially thought to be his final international appearance as Chiellini announced his retirement from the national team.

On 11 January 2018, Chiellini was named to the 2017 UEFA Team of the Year. He made his 350th appearance in Serie A in a 0–0 away draw against S.P.A.L., on 17 March.

On 29 June 2018, Chiellini was given a two-year contract extension until 2020 and also named the club’s new captain after the departure of Buffon.

On 17 March 2018, despite Chiellini’s initial decision to retire, he was called up for the March 2018 friendlies against Argentina and England by interim manager Luigi Di Biagio. After sustaining an injury, however, he was dropped from the squad, and Angelo Ogbonna was called up in his place.

He was once again called up to the national team in September 2018, by manager Roberto Mancini, for Italy’s opening UEFA Nations League matches against Poland and Portugal later that month. Chiellini was also named the new captain of the Italian national team following Gianluigi Buffon’s international retirement. He subsequently wore the captain’s armband in Italy’s 1–1 home draw against Poland on 7 September, in their UEFA Nations League opener. On 11 October, he made his 98th appearance for Italy in a 1–1 friendly draw against Ukraine in Genoa, equalling Gianluca Zambrotta as his nation’s joint-seventh highest appearance holder of all time. On 17 November, he made his 100th appearance for Italy in a 0–0 draw against Portugal at the San Siro stadium in Milan, in his team’s final UEFA Nations League match.

Regarded as a promising defender in his youth, he came to be considered as one of the best defenders in world football, one of the greatest defenders of his generation, and one of Juventus’s greatest defenders ever. In 2018, his Juventus manager at the time – Massimiliano Allegri – described him as “the best defender in the world.” Regarding Chiellini’s strength and man-marking ability, his former Livorno manager Walter Mazzarri once labeled him as “a force of nature”, also adding “he’s a universal player that any coach would love to have on his team. He is from another planet; he can mark three players by himself.”

A popular figure with fans, he is also known for his dedication and vocal leadership on the pitch, and was Juventus’s long-time vice captain, behind Gianluigi Buffon; following Buffon’s departure in 2018, Chiellini was appointed the team’s new captain. Although he is not known for his pace over short distances, he is also a mobile defender. Moreover, he possesses a strong mentality, good temperament under pressure, determination, and excellent concentration, as well as an ability to organise his back-line. Despite his ability as a defender, he has often struggled with injuries in recent seasons.

On 16 January 2019, Chiellini lifted his first title as Juventus’s new official captain – the Supercoppa Italiana – following a 1–0 victory over Milan. On 12 March, Chiellini marked his 500th appearance in a Juventus jersey with a 3–0 win home to Atlético Madrid in the Champions League round of 16 second leg to overturn a 2–0 deficit to reach the quarter-finals. Juventus ended the season as league champions, with Chiellini capturing his record eighth Serie A title with the club.

On 24 August, in Juventus’s opening match of the 2019–20 season against Parma, Chiellini scored the only goal of the match in a 1–0 away win in Serie A. On 30 August, Chiellini tore his anterior cruciate ligament during training. He returned on 16 February 2020, in a match against Brescia, replacing Leonardo Bonucci in the 78th minute. On 29 June, Chiellini signed a new contract with Juventus, extending until June 2021.

On 20 October 2020, Chiellini made his 71st Champions League appearance with Juventus in the team’s opening European game of the season, a 2–0 away win over Dynamo Kyiv, overtaking Alessio Tacchinardi as the club’s third–most capped player of all time in the competition; however, he suffered an injury during the first half and was replaced by Merih Demiral.

In 2020, Chiellini released his autobiography Io, Giorgio, with the profits goint to the insuperabili charity during the COVID-19 pandemic in Italy. However, Chiellini attracted controversy due to his strong criticism of his former club and international teammates Felipe Melo and Mario Balotelli in his book.