O'Grady has participated in the Tour de France since 1998, and he has contended for the prestigious sprinters' maillot vert (green jersey) on several occasions, finishing second in the 1998, 1999, 2001 and 2005 editions of the race. He has also worn the maillot jaune (yellow jersey) of the race leader in the 1998 and 2001 edition of the Tour. He currently rides for Team CSC in the UCI ProTour road racing series and is contracted to them through to 2008.
When it was time to turn professional, he joined the GAN team (now Crédit Agricole), which at the time included English time trial specialist Chris Boardman.
In the 1998 Tour de France he wore the race leader's maillot jaune (yellow jersey) for three days. He also won his first stage of the race. Again in 2001, he rode in the yellow jersey, this time for five days, and Stuart O'Grady was named Australian Cyclist of the Year and Australian Male Road Cyclist of the Year in both 1998 and 2001. In 1998 he finished second overall in the sprinters' green jersey classification. In 2001, O'Grady had been in contention for the sprinters green jersey in competition with Erik Zabel from Germany, but he was defeated on the final day's racing in the streets of Paris.
In 2001 he was diagnosed with a narrowing in the iliac artery, after early tests established that his right leg produced more power than his left leg. After a surgery in the April 2002, he started a new rehabilitation program to get back into racing form by the summer, and O'Grady was again in contention in the 2002 Tour de France. In 2003 and 2004 he was overshadowed in the green jersey competition by fellow Australian sprinters Baden Cooke (2003) and Robbie McEwen (2004). O'Grady still managed to win his second Tour de France stage win at the 2004 Tour De France.
O'Grady moved to the Cofidis team in 2004, intending to put emphasis on the Spring classics races such as Paris-Roubaix and Ronde van Vlaanderen. After a near-disastrous start to the season, fraught with injuries and doping allegations in his team, he made a comeback by winning two stages and the points classification in the Dauphiné Libéré race. He continued with a stage win in the 2004 Tour de France, where he also spent a few days in the green jersey. He rounded his road racing season off by winning the UCI Road World Cup race HEW Cyclassics. He topped his list of victories by winning an Olympic gold medal in the Madison cycling with Graeme Brown.
In the 2005 Tour de France, O'Grady came second in the green jersey classification to Thor Hushovd of Norway, closely followed by Robbie McEwen in 3rd place. Late in 2005, he signed a one-year contract with Bjarne Riis to ride on Team CSC for 2006. However, his 2006 season was plagued with injury, breaking several ribs in an early season race in Italy and fracturing a vertebra in the Tour de France. O'Grady continued riding the Tour despite the considerable pain caused by the fracture, coming third in the sprint for the final stage.
Coming back from a difficult 2006, early in 2007 O'Grady achieved his career highlight in becoming the first Australian to win a European Cycling Classic when he crossed the line first in the cobbled classic Paris-Roubaix. He began the day as support team mate and 2006 winner Fabian Cancellara but following a puncture midway through the race, he recovered to rejoin the main field before passing them and arriving alone in the Roubaix veledrome.
In the 2007 Tour, O'Grady was forced to abandon on Stage 8 from Le-Grand-Bornand to Tignes after crashing on a descent, fracturing five ribs, his right shoulder blade, right collar bone, three vertebrae and puncturing his right lung.
O'Grady is a very keen Port Adelaide Power supporter in the AFL. He once held the title of the clubs No. 1 ticket holder and very regularly watches the matches.
O'Grady has also set up and financially supports an Australian junior cycling development team, CSC Team O'Grady.
O'Grady successfully teamed with Graeme Brown to win a gold medal with 22 points in the Madison cycling event at the 2004 Summer Olympics in Athens. (See Cycling at the 2004 Summer Olympics)
He has attended the three previous Olympics, representing Australia: 1992, Barcelona