Nakagami joined the Japanese Road Race Championship in 2005 and returned the following year to win the GP125 title, becoming the youngest-ever Japanese 125cc champion — a feat he achieved by winning every race of the 2006 season. He also joined the MotoGP Academy that year, gaining international experience in the Spanish CEV 125cc series.
After two years in CEV competition, Nakagami contested the 125cc World Championship from 2008 to 2009, scoring a best finish of eighth. He then returned to Japan to compete in domestic championships, winning the Suzuka 8 Hours in 2010 and claiming the J-GP2 title in 2011, winning five of six races.
Nakagami made his Moto2 debut as a substitute in 2011 before joining Italtrans Racing Team full-time in 2012, finishing 15th in his debut season. His 2013 campaign with Italtrans was breakthrough, delivering four podium finishes — including four consecutive second-place results at Indianapolis, Brno, Silverstone, and Misano — and three pole positions. He finished eighth in the championship with 149 points.
He then joined Idemitsu Honda Team Asia for 2014, enduring a difficult year with a disqualification that cost him a strong result. In 2016 he scored his first Moto2 victory at Assen, adding three third-place finishes to end the season sixth overall, his best result in the class. He won again at Silverstone in 2017. His consistent performances over six Moto2 seasons earned him a MotoGP promotion with LCR Honda.
Nakagami joined LCR Honda in 2018 on year-old machinery and completed a steady rookie season, accumulating 33 points for 20th in the championship. In 2019, he showed improvement in the first half of the season with regular top-10 finishes, but a heavy crash at the Dutch TT and subsequent shoulder surgery brought a premature end to his year after the Japanese Grand Prix. He finished 13th with 74 points.
The 2020 season proved to be Nakagami's strongest in MotoGP. With factory-level injuries sidelining Marc Marquez after just the second round, Nakagami emerged as Honda's most reliable performer in the first half of the year, consistently finishing in the top ten and scoring all of the manufacturer's championship points in the opening eight rounds. At the Teruel Grand Prix he qualified on pole position — the first Japanese rider to achieve a MotoGP pole in nearly 16 years. He ended the year tenth in the championship with 116 points.
From 2021 Nakagami received factory-specification Honda machinery, but the RC213V became one of the most problematic bikes in MotoGP during this period. Despite a best result of fourth place in Jerez in 2021, he could only manage 15th in the standings. The following three seasons were similarly constrained by the Honda's uncompetitiveness — he finished 18th (48 points) in 2022, 18th (56 points) in 2023, and retired from full-time racing after 2024 to move into a testing and liaison role for Honda.
Nakagami's seven-year tenure in MotoGP made him the most experienced Japanese rider in the sport's premier class in the modern era. While his results were limited by machinery circumstances, his professionalism and role in Honda's development programme drew consistent respect in the paddock. He made a wildcard return at the 2025 French Grand Prix, finishing sixth in a weather-affected race. From 2025 he acts as test rider and team liaison between Honda's Japanese and Italian MotoGP operations.