With a quick uphill burst, Chris Horner of Bend, Ore., rode away from teammate Levi Leipheimer in the final two miles and pedaled into the race lead at the Tour of California on Wednesday.
Horner (RadioShack), who last year finished 10th in the Tour de France as the top American, completed the 81.8-mile Livermore to San Jose road race in 3 hours, 27 minutes and 51 seconds.
Andy Schleck (Leopard-Trek) of Luxembourg, the 2009 and 2010 Tour de France runner-up, finished second, 1 minute and 15 seconds behind.
Rory Sutherland (United Healthcare) of Australia was third, just behind Schleck.
Horner, who finished fourth overall last year in the Tour of California, leads the seven-day race by 1:15 over Leipheimer of Santa Rosa, the three-time race winner.
Tom Danielson (Garmin-Cervelo) of Boulder, Colo., is third overall, trailing by 1:22.
Leipheimer, who has won five stages of the event, all time trials, finished fourth in the stage, also trailing by 1:15.
"I was riding in support of Levi (Leipheimer); I always gave him room," said Horner, who began his pro career in 1995 and is the second-oldest rider in the race.
"He's the three-time winner of the race and is still a big favorite in the time trial. I think we can go 1-2 overall."
With teammates providing support through the stage, which included four categorized climbs, Horner waited until the base of the final 3.5-mile climb to the finish to launch his move.
Leipheimer followed, but it was soon apparent Horner was the strongest rider.
"I wanted to break the race apart," Horner said following the first mountaintop finish in the six-year race's history.
Schleck, who has finished second to Alberto Contador of Spain in the Tour de France, was expected contest for the stage win.
"I was surprised," said Schleck, sixth overall, trailing Horner by 1:30. "I didn't expect myself to be up there."
The stage's severity took its toll. Four riders didn't finish and nearly half of the field finished more than 24 minutes behind the winner.
Will Dugan of the United States and Michael Matthews of Australia did not start the stage after crashing in stage three. One hundred thirty-eight of the starting field of 144 remain.
The seven-day race continues Thursday with a 135.1-mile Seaside to Paso Robles road race, the longest stage.