Rolfo entered the Grand Prix series with wildcard appearances beginning in 1996. After placing third in the European championship in 1997, he commenced his first full World Championship season in 1998. Progress was gradual in his opening seasons: his best results in 1998 and 1999 were fifth-place finishes at Argentina and Catalunya respectively, while 2000 brought no finish higher than sixth.
The 2001 season marked a breakthrough. Racing for the Safilo Aprilia team, Rolfo claimed three podiums — second at Mugello and Donington Park, third at Catalunya — and finished fourth in the championship. In 2002 with Fortuna-Honda Gresini he scored five second places, three of them behind champion Marco Melandri, and ended the year third overall.
His finest Grand Prix season came in 2003, when he moved to a team run by Daniel Amatrian while retaining Fortuna sponsorship. Rolfo won at Sachsenring and Phillip Island and entered the final round with a mathematical chance at the title. Victory would have given him the championship had Manuel Poggiali finished second or lower, but Rolfo could only manage seventh, ceding the title. He nonetheless finished second overall, ahead of Toni Elías.
In 2004, a lone victory at Catalunya was not enough to sustain his title challenge, and he slipped to eighth overall.
Rolfo stepped up to the premier MotoGP class in 2005 with the D'Antin Ducati team. Racing year-old machinery on Dunlop tyres without a teammate, conditions were far from ideal. He scored points in nine races with a best result of tenth, finishing 18th overall. No MotoGP seat materialised for 2006.
From 2006 onward, Rolfo competed in the Superbike World Championship (WorldSBK). His debut season was with the Caracchi Ducati privateer outfit: a promising start with a fifth and two seventh places early in the year faded, and he ended 16th overall.
In 2007 he joined the HANNspree Ten Kate Honda team alongside 2004 champion James Toseland. Rolfo achieved career-best fourth-place finishes at Monza and Silverstone and placed eighth in the championship, though he was overshadowed by Toseland's title win. He moved to Althea Honda for 2008, taking Hannspree sponsorship with him, but missed the Monza round through injury and was released for 2009 before the season concluded.
For 2009, Rolfo signed with the new-to-WorldSBK Stiggy Racing Honda team alongside Leon Haslam, but lost his place to John Hopkins after the opening Qatar round.
Rolfo also made appearances in the Supersport World Championship (WorldSSP) across various points in his career, adding to his record as a versatile competitor across multiple two-wheeled disciplines.
Roberto Rolfo's career arc — from a near-miss 250cc world title to stints with established WorldSBK outfits — reflects the competitive progression many Italian Grand Prix riders of his generation followed. His 2003 250cc season remains his career highlight, a campaign that produced two race victories and brought him within reach of a world championship until the final round.