Capirossi made his World Championship debut in 125cc in 1990 with the Polini Honda team, claiming his first title that year aged just seventeen years, five months and thirteen days — making him the youngest world champion in motorcycle racing history at the time. He defended the 125cc title in 1991, taking five pole positions and twelve podiums from thirteen rounds, before graduating to the 250cc class.
In the 250cc class, Capirossi was a persistent podium contender across several seasons. He took victories at the Netherlands, San Marino, and United States Grands Prix in 1993, finishing four points behind champion Tetsuya Harada. After a stint in the 500cc Premier Class in 1995 and 1996, he returned to 250cc and claimed the 1998 world championship in controversial circumstances: at the season-deciding Argentine Grand Prix, Harada — who was ahead in second place on the final lap — was struck from behind by Capirossi's machine at the final corner, sending Harada off track and delivering the title to Capirossi following an appeal. Aprilia released him at the end of the season.
Capirossi graduated to the 500cc Premier Class in 1995. After returning from 250cc in 1999 with Honda and then rejoining the 500cc grid in 2000, he made his most significant mark in the MotoGP era following Ducati's arrival. In 2003 he delivered Ducati their first Grand Prix victory at Barcelona, finishing fourth overall in the championship. Through 2005 and 2006 he was among Ducati's strongest performers, winning races in Japan, Malaysia, and Jerez, and briefly sharing the MotoGP standings lead with Nicky Hayden in 2006 before finishing third overall that year.
In 2008 and 2009 Capirossi rode for the Suzuki factory team alongside Australian Chris Vermeulen, but results were modest — his sole 2008 podium came at Brno. His 2009 campaign produced no podium finishes, the first time since 1992 he had finished a full season without one. On 11 April 2010, Capirossi became the first rider in Grand Prix motorcycle racing history to start 300 races, achieving the milestone at the season-opening Qatar Grand Prix.
For 2011, Capirossi joined the Ducati Pramac satellite team. On 1 September 2011 he announced his retirement from MotoGP racing, to take effect at the end of that season, concluding a 22-year Grand Prix career spanning 300-plus starts. His race number, 65, was officially retired from all classes of Grand Prix motorcycle racing in November 2016, a mark of recognition rarely bestowed.
After retirement, Capirossi took on the role of Safety Advisor to Dorna Sports, working with the MotoGP Safety Commission to improve conditions and protocols for riders. His experience across multiple eras of Grand Prix machinery made him a respected voice on circuit safety and regulatory matters.
Capirossi stands as one of the most versatile Grand Prix motorcycle racers of his generation: a triple world champion across three classes, a nine-time Premier Class race winner, and the sport's first 300-race starter. His career bridged the two-stroke era and the transition to four-stroke MotoGP machinery, and his longevity at the top level — competing from 1990 through 2011 — remains one of the longest tenures in Grand Prix motorcycle racing history.