A product of the Red Bull MotoGP Academy initiative, Nakagami became the youngest ever winner of the Japanese 125cc Championship in 2006, and in 2007 he entered the Spanish series under the Academy banner. In the World Championship in 2008, he achieved his best result of the year with a top ten finish at Donington and he continued in the Championship in 2009. Stepping away from the World Championship for two years, he won the Japanese Moto2™ title in 2011 and was drafted in by the Italtrans team at the Japan GP as a substitute rider. The team offered him a full-time seat for 2012, and in 2013 just missed out on a maiden race victory on numerous occasions - not least when he scored four consecutive second place finishes in the middle of the season. He switched to Idemitsu Honda Team Asia for 2014 but had a tough year, before a return to the podium with third in Misano the following year. He remained with the team in 2016 and took his first win in Assen at the Dutch GP, and by the end of 2017 had garnered eight podiums and two poles.

For 2018 Nakagami graduated to the premier class to ride with LCR Honda Idemitsu, and was the best qualifying rookie with several appearances in Q2. 2019 saw Nakagami stay with LCR Honda Idemitsu on a 2018 RC213V, and the Japanese rider strung a solid season together, claiming nine Top 10s and a best finish of P5 at Mugello. Shoulder surgery ended Nakagami’s season after the Japanese GP. His fourth season in the premier class saw him improve even further, placing inside the Top 10 in every race with the exception of Teruel, where he earned a first pole position, and the Valencia GPs. Another year with LCR but it was another of missed opportunity for Nakagami. HRC's struggles certainly didn't help but crashes in key moments saw the Japanese rider end the year with two top five finishes. It was the same story in 2022 as Honda's radically new machine failed to deliver an upturn in results. A best finish of seventh saw him fighting for his future in 2023, and despite another difficult season that brought a best finish of P8, Nakagami's efforts were rewarded with one more year with IDEMITSU Honda LCR in 2024.