Takahashi's development was shaped by the HRC Racing Scholarship, a Honda programme designed to bring young Japanese riders into world-level competition. He made his first wild card appearance in the 125cc World Championship at the Japanese Grand Prix in 2001. Between 2002 and 2004 he made four wild card starts in the 250cc World Championship at his home round, finishing in the top five on all four occasions. In 2001 he was runner-up in the MFJ All Japan Road Race GP125 Championship, and in 2004 he won the MFJ All Japan Road Race GP250 Championship.
Takahashi became a full-time 250cc World Championship competitor in 2005, finishing eleventh overall in his debut season on a Honda. In 2006, despite Honda ceasing development of their two-stroke 250cc machine, Takahashi took two wins and finished sixth overall. He slipped to eleventh in 2007 as the team began to struggle, but rebounded strongly in 2008, taking three podium finishes and completing the year fifth overall — his best 250cc championship result. At the Valencia finale that year he qualified tenth and finished second.
For the 2009 MotoGP season, Takahashi was given a premier-class ride by the JiR Team Scot on a Honda RC212V, effectively replacing Andrea Dovizioso who had moved to the Repsol Honda factory team. Takahashi faced a difficult start to his MotoGP career. His best result in the early rounds was twelfth at the Circuit de Catalunya. He also suffered an early collision with Nicky Hayden at the Japanese Grand Prix. On 1 July 2009, Team Scot announced it was terminating his contract due to financial constraints after just seven rounds; he was replaced by Hungarian rider Gábor Talmácsi. His departure left no Japanese rider in the premier class for the remainder of the season — a situation not seen since 1991.
Takahashi dropped into the new Moto2 class for 2010 alongside Raffaele de Rosa at Tech 3. He claimed his first Moto2 victory at Barcelona, benefiting from a ride-through penalty imposed on Andrea Iannone, and ended the season twelfth overall. For 2011 he signed with Gresini Racing on a Moriwaki, taking two podium finishes and finishing eleventh. In 2012 with NGM Mobile Forward Racing he rode a Suter for the first six rounds and an FTR for the remainder, scoring only a single points finish across the season. In 2013 he joined IDEMITSU Honda Team Asia on a Moriwaki run by Tadayuki Okada, but failed to score a point in the first eleven rounds and was replaced by Azlan Shah Kamaruzaman from Misano onwards.
After his Grand Prix career concluded, Takahashi returned to domestic competition in Japan, contesting the All Japan Road Race JSB1000 Championship aboard a Honda CBR1000RR.
Yuki Takahashi's career illustrated both the potential of the HRC Scholarship pathway and the difficulty Japanese riders faced in sustaining themselves in the financially precarious mid-field of MotoGP. His five-place finish in the 2008 250cc standings and his Barcelona Moto2 win remained the high points of an international career conducted almost entirely under the Honda umbrella.