Tejay van Garderen took the overall lead as the race split in the final third of the 185.7km stage from Santa Barbara with overnight leader Janier Acevedo (Jamis-Hagens Berman) distanced by strong crosswinds.
Voigt's RadioShack Leopard team-mates started the acceleration and 16 riders at the front quickly built a lead that grew to 50 seconds with 38km to go.
The breakaway was pegged back to 30 seconds with 22km left, but the leaders picked up the pace again and eventually stretched the gap out to more than a minute by the finish.
41-year-old German van Garderen smelled the possibility of victory and blasted off the front to time trial into the finish line, collapsing against the barriers in exhaustion after coming home six seconds ahead of Tyler Farrar (Garmin-Sharp) and Thor Hushovd (BMC).
“We had a close look at the road circuit today and saw at 125km into the race when the road turned just a little bit, and the headwind switched to a crosswind, that we could do something there," said Voigt.
"Markel Irizar and I were in the front to drive the break, and after a while Markel said to me, ‘I think you look really good today so maybe you should save something for the end.’ I thought about it and agreed. There were some quality riders in the group. To win from that group, I knew I would have to go alone.
"I had hopes they would look at one another to chase me and give me 20 seconds. Once you do that, I’m gone. Once I went and then looked back to see the gap, I couldn’t believe they had given me 20 seconds. I said to myself, ‘Yes!’ It was pretty hard and I really had to dig deep. I’m a happy stage winner.”
Heading into Friday's 31.6km individual time trial, van Garderen leads 2010 Tour of California winner Michael Rogers (Team Saxo-Tinkoff) by 42 seconds while Acevedo is third, 50 seconds back.
"At the beginning of the day, nothing suggested today would be anything more than a bunch sprint and a non-GC (general classification) day," van Garderen said.
"But nobody can really predict the weather and that's cycling. You always have to be attentive and luckily our guys were."
Van Garderen said wearing the race leader's yellow jersey will not change his approach to the race against the clock that finishes with a three-kilometre climb.
"You go in and ride as best as you can and as hard as you can," he said. "Right now all my focus is on the time trial. We'll deal with Mt. Diablo (Saturday's mountain-top finish) when we get there."
- Sports & Recreation
- Tejay van Garderen
- Janier Acevedo
- Markel Irizar