Floyd Landis set off in the yellow jersey on the final stage of the Tour de France on Sunday.
Barring accident or mishap, Landis was expected to win the race and become the third American champion of cycling's showcase event.
Landis began the 154.5-kilometer (96-mile) route from Sceaux-Antony to the tree-lined streets of Paris' Champs-Elysees with a 59-second lead over Oscar Pereiro. He is also 1:29 ahead of Andreas Kloeden of Germany.
Fellow American Lance Armstrong won seven Tours and compatriot Greg Lemond won it three times.
"I look forward to seeing him up on the podium in Paris," Armstrong said in a statement on Sunday. "If it couldn't be one of my guys from Discovery Channel then I am thrilled to see Floyd continue the success of American cycling."
Former Tour cyclist Laurent Jalabert said, "American cyclists bring a sense of professionalism and dedication to racing."
Landis was a former teammate to Armstrong on his three Tour wins from 2001-04. He joined the Phonak team in 2005 and placed ninth on last year's Tour.
At the start line, Landis joked with Robbie McEwen, the likely winner of the green jersey awarded to the best sprinter, and Mickael Rasmussen, who was sporting the red polka-dot jersey as the best climber.
Rasmussen was the best climber in 2005, while McEwen was the green jersey winner in 2002 and 2004 - the year Kloeden finished second overall behind Armstrong.
On his final stage as Tour director, Jean-Marie Leblanc sat in the No. 1 Tour car alongside Eddy Merckx, the five-time winner of the race and arguably the greatest cyclist of all time.
Leblanc's first Tour was in 1989 when Lemond beat Laurent Fignon of France by just 8 seconds in a sprint on the Champs-Elysees. On Saturday, Landis regained the yellow jersey after finishing third in the time trial.