Caruana lost the World Chess Championship to Magnus Carlsen in the rapid tiebreaks after drawing all twelve of the classical games.

[4] Until the age of twelve, he lived and played in the United States, occasionally traveling to Europe and South America to participate in tournaments.

He obtained his final GM norm and at age 14 years, 11 months, and 20 days, became the youngest grandmaster of both the United States and Italy, surpassing the US record set by Hikaru Nakamura.

In June Caruana played first board for Italy at the Mitropa Cup, which is a four-board team competition amongst 10 "middle" European nations.

In his group, Caruana placed first with a score of +4 (5½/7) winning against Maxime Vachier-Lagrave, Xiangzhi Bu, Alexandra Kosteniuk, Marie Sebag, and drawing against Vasyl Ivanchuk, Ivan Cheparinov, and Kateryna Lahno.

[12] When winter rolled around in November and December, Caruana successfully defended his title winning the Italian Championship for the second consecutive year with a score of +5 (8/11).

In May he played with the Italian team in the "Mitropa Cup" at Rogaska Slatina in Slovenia, scoring 6 points out of 8 and winning the individual gold medal on first board.

In July, Caruana won the Young Grandmaster Section of Biel 2010 after a playoff with the others two leaders Maxime Vachier-Lagrave and Nguyễn Ngọc Trường Sơn.

[23] In April at the third stage of the FIDE Grand Prix Series 2012–2013 held in Zug, Switzerland, with six points out of 11 games, Caruana shared third place with Ruslan Ponomariov, behind the winner, Veselin Topalov, and the runner-up, Hikaru Nakamura.

[24] In May–June at the fourth stage of the "FIDE Grand Prix Series 2012–2013" held in Thessaloniki, Greece, Caruana shared second place with Gata Kamsky, behind the winner, Leinier Domínguez Pérez.

[25] In June at the eighth edition of the Tal Memorial Chess Tournament, held in Moscow, Caruana, with five points out of nine games, finished third after tiebreak with Shakhriyar Mamedyarov and Dmitry Andreikin, behind the winner, Boris Gelfand, and the runner-up, Magnus Carlsen.

[28] In January, at the Tata Steel Chess Tournament in Wijk aan Zee, Netherlands, Caruana finished fourth with 6 points out 11 games.

[30] In FIDE World Blitz Championship, also held in Dubai, Caruana finished in the middle of the group, confirming some difficulties with short time control.

[34] In the period of late October through early November, Caruana shared fourth place with six points out of 11 games at the Tashkent leg of the FIDE Grand Prix.

In January, Caruana played in the 2015 Tata Steel Chess Tournament, a 14-player round-robin, where he finished seventh, with seven points out 13 games, behind the winner Magnus Carlsen.

In April at the Shamkir Chess 2015, a 10 players tournament, Caruana finished fourth with five points out of nine games behind the winner Magnus Carlsen.

The lineup of the tournament included Viswanathan Anand, Hikaru Nakamura, Sergey Karjakin, Peter Svidler, Veselin Topalov, Anish Giri, and Levon Aronian.

He played the Tradewise Gibraltar Chess Festival in March and finished with a score of 7/10, suffering one loss to Nigel Short in Round 6.

The World Cup tightened the race between Caruana, Wesley So, and Vladimir Kramnik for the two ratings qualification spots to the 2018 Candidates Tournament to within a few points.

Kramnik's surprise loss to James Tarjan, who quit chess for a few decades to become a librarian, further helped solidify Caruana and So as the ratings qualifiers.

[43] In December 2017 with the Candidates qualification already decided, Caruana rebounded and won his only tournament of the year at the London Chess Classic in tiebreaks.

[44] In March, he won the Candidates Tournament 2018 with a score of 9/14, thus winning the right to challenge Magnus Carlsen in the World Chess Championship 2018 in London in November 2018.

[52] In January, he won the Category 20 2020 Tata Steel Masters with a round to spare, scoring 10/13 (+7–0=6), two points ahead of second-placed Magnus Carlsen.

[71] Apart from the events he played, Caruana also participated in the coverage of the World Chess Championship 2021 in November and December 2021, along with Daniel Rensch and Robert Hess, for Chess.com.

[73] In April 2022, he won the inaugural American Cup, a double-elimination tournament in Missouri, ahead of Levon Aronian, Wesley So, and Lenier Dominguez.

[74] From June 16 to July 5, Caruana participated in the Candidates Tournament held in Madrid, having qualified to play by being the runner-up in the Grand Swiss in 2021 behind Alireza Firouzja.

[81] The next month, Caruana participated in the Sinquefield Cup, finishing tied 3rd alongside compatriot Wesley So with 4.5/8 points[g] and behind runner-up Ian Nepomniachtchi and winner Alireza Firouzja.

He scored wins against Alireza Firouzja, Wesley So, and Richárd Rapport en route to his victory, where he earned $100,000 and 13 Grand Chess tour points.

"[5] Caruana's playing style is now universal, based on opening preparation and calculation: "I wouldn't assess it in such categories [tactical or strategic].

"[32] Talking about Magnus Carlsen's play, Caruana hinted at his deep knowledge of the opponent's strengths and weaknesses: "In some positions you can't compete with him.