Kallio began racing in 1997 and quickly accumulated national success in Finland, winning the Finnish road racing championship in 1998, 1999, and 2000, and the Nordic championship in 2000. He also excelled in motorcycle ice racing, claiming Finnish championships in 2000, 2004, and 2005 at 125cc level and in 2004 and 2006 at 500cc.
Kallio debuted in the 125cc World Championship as a wildcard at the 2001 German Grand Prix with the Finnish Ajo Motorsport team, riding a Honda RS125R. He earned Rookie of the Year honours in 2002, finishing 11th in the standings with 78 points. His 2002 rookie class included Héctor Barberá, Andrea Dovizioso, and Jorge Lorenzo.
Midway through the 2003 season, after outperforming factory KTM rider Arnaud Vincent, Kallio was promoted to Red Bull KTM's factory squad. He immediately scored his first 125cc podium — a second place at Sepang behind Dani Pedrosa — and finished the year 11th overall with 88 points. For 2004 Red Bull KTM also signed 2003 Rookie of the Year Casey Stoner alongside Kallio, but reliability problems plagued both riders throughout the season.
The 2005 season was Kallio's breakthrough year. He took his first championship pole position and victory at Estoril, went on to accumulate seven pole positions — five of them consecutive, both class records at the time — and won again in Germany and Japan. His title challenge collapsed in Qatar, where teammate Gábor Talmácsi overtook him on the final straight in the closing meters of the race, winning by 0.017 seconds. Talmácsi later claimed he thought there was one more lap remaining. The lost five points proved decisive: Kallio could only finish fifth in Australia, retired in Turkey, and went into the Valencia finale 23 points behind Thomas Lüthi. Kallio won that final race but Lüthi finished ninth, leaving Kallio five points short of the championship. Both riders had four wins, but Kallio would have had five, and thus won the title on countback, had the Qatar incident not occurred. Talmácsi was dismissed from the team after Valencia.
In 2006 Kallio produced his career-best 125cc season, scoring three victories in Shanghai, Assen, and Motegi, recording four pole positions, and finishing on the podium eleven times. He again claimed the runner-up position in the championship, this time behind dominant champion Álvaro Bautista, though he finished a full 65 points clear of third-placed Héctor Faubel. Finnish motorsport viewers voted him Finnish Motorsportsman of the Year for the second consecutive year.
Kallio moved to the 250cc class with KTM for 2007, partnering Hiroshi Aoyama. Despite early mechanical difficulties, he took his debut 250cc podium and pole position at the Sachsenring and secured two victories — at Japan and Valencia — to finish seventh overall in his rookie season. In 2008, an exceptionally strong opening stretch saw him win at Jerez (after championship rivals Bautista and Marco Simoncelli crashed out on the final lap), Portugal, and China, building a championship lead. However, reliability problems eroded his advantage, and Simoncelli won the title, with Bautista second and Kallio third overall.
For 2009 Kallio moved to the premier class with Pramac Ducati alongside Niccolò Canepa, receiving the latest-spec Desmosedici GP9. He collected 71 points, earned the MotoGP Rookie of the Year award, and was called to replace the injured Casey Stoner at the factory Ducati squad for three races, finishing eighth at Indianapolis and seventh at Rimini. His 2010 MotoGP campaign with Pramac was difficult, yielding only two top-ten finishes before a shoulder injury ended his season early.
Kallio dropped to Moto2 with Marc VDS Racing for 2011. After a difficult first half he finished second at Valencia in the season's final round. A stronger 2012 campaign ended with him sixth overall. In 2013 he scored his first Moto2 victory at the Czech Republic Grand Prix in a race-long battle involving Takaaki Nakagami and Thomas Lüthi, and finished fourth in the championship with 188 points.
The 2014 season represented the peak of Kallio's Moto2 achievements. Partnered with Esteve Rabat at Marc VDS, he won at Jerez and Le Mans in consecutive races, then scored a dominant pole-to-flag victory at Indianapolis — with pole, fastest lap, race win, and leading every lap — his 16th career win, surpassing Jarno Saarinen's tally to become Finland's most successful race winner in Grand Prix motorcycle racing history. He entered the final rounds with a genuine title chance but Rabat's momentum proved decisive, and Kallio finished runner-up in the championship with three wins and a personal-best 288 points.
A frustrating 2015 campaign with Italtrans, including a mutual contract cancellation midseason, was followed by a late-season stint with QMMF Racing on a Speed Up machine.
KTM confirmed Kallio as their lead MotoGP test rider in October 2015. He received wildcard race entries in 2016 and 2017, including an impressive tenth-place finish at KTM's home Austrian Grand Prix in 2017 — the first time a KTM had finished a premier class race within twenty seconds of the race winner. A serious knee injury in 2018 at the Sachsenring disrupted the KTM test programme. In 2019 Kallio replaced the injured Johann Zarco mid-season, scoring seven points in six races. In late 2020 he replaced Iker Lecuona — who had tested positive for COVID-19 — for two Valencia rounds and the Portuguese Grand Prix.
Kallio's career is defined as much by near-misses as by victories. The 2005 Qatar incident remains one of the most discussed episodes in 125cc history, a single race that reordered the championship. His record as Finland's most prolific Grand Prix winner and his sustained excellence across 125cc, 250cc, Moto2, and MotoGP establish him as one of the sport's most complete and durable competitors.