Van Garderen, the 24-year-old BMC rider who grew up in Bozeman, Mont., completed the 19.6-mile route in 48 minutes, 49 seconds. He was the last of 112 riders on the hilly and technical course in the sixth stage.
"I don't want to count my chickens before they hatch, but I'm ready to win, and I think it's about time," said van Garderen, who finished fifth in the event in 2011 and fourth last year. I think now I'm finally mature enough to pull through to the end. I think I'm ready to do it."
Dutchman Lieuwe Westra of Vacansoleil-DCM, the stage one winner, was second in 49:15.
Australia's Rohan Dennis of RadioShack Leopard was third in 49:20.
Van Garderen, who took the race lead with a 10th-place finish in the fifth stage, leads Rogers, the Saxo-Tinkoff rider and three-time world time trial champion, by 1:47 seconds with two stages left in the eight-day race. Rogers finished fourth in the stage, 1:05 behind van Garderen.
Rogers and several other top contenders opted to switch from time trial to road bikes to negotiate the steep final climb.
"It was a steep climb, I think for me maybe too steep for the time trial bike, the gearing was more suitable on the road bike," said Rogers, the 2010 Tour of California winner. "It was a perfect climb because it was steep straight away, and the speed dropped very fast. I took advantage of the speed being low and changed," he said.
Van Garderen remained on his time trial bike the entire route.
"There was really no place that you could hold back," said van Garderen, who was fifth last year as the highest-finishing American in the Tour de France. "I started straightaway up that climb. You just had to dig deep there. The climb up to the finish was hard. There was a couple of little downhills that you could kind of soft-pedal and catch your breath a little bit."
Australia's Cameron Meyer of Orica GreenEdge jumped from sixth to third overall with a sixth-place finish in the stage. He trails van Garderen by 2:57.
American Dave Zabriskie, the four-time Tour of California race runner-up, crashed out of the event while training on the time trial course.
The eight-day event continues Saturday with the 91.4-mile stage from Livermore to Danville. The route will finish with an 11.5-mile ascent to Mount Diablo
The 727-mile race concludes Sunday with an 80.7-mile morning road race from San Francisco to Santa Rosa.