Born in Granollers, Barcelona, Espargaró began competing in the 125cc World Championship in 2006, participating in the last six races of the year as a replacement for Andrea Iannone at Campetella Racing. Prior to this, he made history at the Catalan Grand Prix as a wildcard, finishing 13th to become the youngest ever point scorer in a Grand Prix at the age of 15 years and 8 days. He followed this by winning five consecutive races in the Spanish 125cc Championship to become champion, and finished 6th at the Valencian Grand Prix.
In 2007, Espargaró competed with Campetella Racing Junior Aprilia for a full season. He achieved a third-place finish at the Portuguese race, battling for the lead with Héctor Faubel and Gábor Talmácsi, finishing just 0.2 seconds behind Faubel. He then switched to a Derbi for the 2008–2010 seasons, achieving 3 podiums and 2 pole positions, and finishing 9th in the championship in 2008.
Espargaró moved to Moto2 in 2011 with the HP Tuenti Speed Up team, finishing 13th with 75 points. In 2012, riding for Pons 40 HP Tuenti, he achieved several podiums and wins, including victories in Spain, Great Britain, and Aragon. He secured six pole positions throughout the season, ultimately finishing 2nd in the championship with 269 points.
The 2013 season saw Espargaró remain with the same team and achieve six wins – in Qatar, Catalonia, Netherlands, San Marino, Australia and Japan – along with a second place in Malaysia and two third places in Germany and Aragon. He also secured six pole positions, ultimately becoming the world champion with 265 points.
In 2018, Espargaró fractured his left collarbone during warm-up for the Czech Republic Grand Prix, forcing him to miss further races in Austria and Great Britain. He suffered a second fracture of the same bone during free practice at the Aragon Grand Prix. Despite these injuries, he achieved his first podium in MotoGP, a third-place finish, at the Valencian Community Grand Prix.
During the 2023 season, Espargaró sustained injuries in a practice crash at the Portimão Circuit, requiring hospitalisation and preventing him from competing in the initial race weekend. He returned to racing as a wildcard at the British Grand Prix in August.
Espargaró won the Suzuka) 8 Hours in 2015 with Bradley Smith and Katsuyuki Nakasuga, becoming the second Spanish driver to win the race after Carlos Checa. He repeated this success in 2016, again with Nakasuga, and also with Alex Lowes.
In 2024, Espargaró was entered as a KTM wildcard rider in the Italian Grand Prix, finishing 17th in the main race. He featured again as a wildcard at the Austrian Grand Prix with 9th in the sprint race, and 11th in the main race. He also raced in Misano, finishing 10th in the main feature race. In 2025, Espargaró was signed as a test and reserve rider for the Red Bull KTM Tech3 team, deputising for Maverick Viñales at the Czech and Hungarian Grand Prix, and again at the Australian and Malaysian Grand Prix.
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