A climber and time trialist, he was selected by Discovery Channel for the 2005 Giro d'Italia and helped Paolo Savoldelli win, although failing to complete the course himself. After 2005 he joined the Swiss team, Phonak. There he began to build some of his best results, finishing fourth in the 2006 Volta a Catalunya and second in the 2006 Canadian time trial championship. Later that season he rode the Vuelta a España, although he dropped out near the end to concentrate on the road world championships in Salzburg. He achieved only modest results. The end of the Phonak team led him to Health Net for 2007. For 2008 he joined Garmin-Slipstream and helped Christian Vande Velde to fifth in the Tour de France.
In 2009 Hesjedal competed in the Vuelta a España, winning the 12th stage. He was the first Canadian to have won a Vuelta stage and the first Canadian individual winner of a Grand Tour stage since Steve Bauer in the 1988 Tour de France. Hesjedal was the only Canadian to compete in the Tour de France for both 2008 and 2009. He was also the first Canadian to ride in the daunting race in more than 10 years.
At the end of the 2009 year Hesjedal was selected as Canadian cyclist of the decade and male Canadian cyclist of the year. The honour was given to him from Canadian Cyclist and the results came from an online poll. He was also named male international cyclist of the year of 2009 from Cycling BC.
During the 2010 Tour de France, Hesjedal finished 4th in the third stage after leading by himself for much of the race until being caught in the last 6 km. He was awarded the most combative rider on the day and thus wore red numbers for the fourth stage. On the 22nd of July 2010 Hesjedal again finished fourth in Tour de France, this time on stage 17 on the famed slopes of the Col du Tourmalet. Hesjedal went on to finish seventh in the 2010 Tour de France, the highest Canadian finish in the TDF in 22 years, when Bauer finished fourth in the 1988 Tour de France. Hesjedal went on to say of his result that “I hope this result does positive things for Canadian cycling and motivates the next generation of Canadian cyclists. I hope that’s the biggest thing that comes out of this...This placing will be there [in the books] forever...If this makes more Canadians aware of cycling, and want to cycle, then it will have been worth it for that alone."