Holcomb, with Justin Olsen, Steve Mesler and brakeman Curtis Tomasevicz wedged in behind him, twice tamed the fury of Whistler with immaculate driving to open a 0.40-second lead over over Lyndon Rush who was at the controls of Canada I.
His second run time of 50.86 was a new Whistler record.
Germany's Andre Lange, bidding for a record third consecutive Olympic gold in the showcase four-man event, was clinging on in third place, 0.44 seconds behind Holcomb.
"We're right where we want to be," world champion Holcomb said. "We had a great day today and we'll have a great day tomorrow. I'm not thinking about 62 years, that's just adding pressure we don't need. Andre's the one under pressure."
"He definitely looked distracted I think but he's a fighter and he won't give up."
Six crashes, all at the same 13th corner appropriately nicknamed 50-50, added to the high-speed sporting theatre and John James Jackson's nightmare Olympic debut continued as the Great Britain quartet suffered a nasty crash in the second run
The foursome of Jackson, Dan Money, Allyn Condon and Henry Nwume began their campaign well enough and placed 11th after heat one, but they could not follow suit on their second run on the lightning fast Whistler track.
Jackson and Money crashed in their opening run of their two-man bobsleigh campaign and again suffered a nasty spill. Medical staff rushed to greet the British quartet but there were no serious injuries, only bruised egos with Money hurling his helmet onto the ice in frustration.
Jackson said the crew aim to return to action for their final runs on Saturday as long as their sled is in good shape.
Jackson said: "I made a mistake, I went a little bit too high on the exit of 11. Obviously we're disappointed, but we're fine.
"We've got a couple of bumps and bruises. The sled has a few scrapes. We'll have a closer look at it later, but if it's fine we'll be back again tomorrow.
"We got some confidence after the first run and I just tried to push it a little bit more on the second," he added.
The event attracted thousands of fans to the Olympic sliding centre on a snowy day on Blackcomb Mountain. Some unfurled huge national flags as they perched around the winding 1400m lay-out long before the start but it was those waving the Stars and Stripes and the red Maple Leaf who had most to cheer as Holcomb and Rush did battle.
Subdued German fans just looked soggy as Lange, bobsleigh's ultimate driving machine, struggled. The gold medallist in the two-man began as favourite to repeat his Turin double but had problems on both runs.
The 36-year-old soldier, the sport's most decorated Olympian, had his sled tottering on one runner at corner 13 but slammed it down just in time - a stark contrast to the smooth Holcomb whose shiny black sled, loaded with 400 kilos of pure American bulk, barely scraped a wall.
Kevin Kuske, brakeman for Lange, said Holcomb would be hard to catch.
"It's going to be really, really difficult," Kuske, who has been brakeman for Lange in four of his five Olympic golds, said.
"What Steve did here today was super-genius. Considering the conditions, he's the best driver on the track right now.
"You're always hoping, but if you drive like Holcomb drove today, you'd be a worthy Olympic champion."
John Napier, driver of America II, rolled his sled over and crossed the finish line upside-down, the crews heads scraping against the walls of the track.
"When you're going at 95mph, if you make a mistake there's no time to catch up," Napier said. "I'm just happy no one was seriously injured and that's a blessing. It's more my ego that's bruised."
Alexandr Zubkov, Russia's Turin silver medallist and bronze medal winner in the two-man in Vancouver, turned over at 13 which at this rate may have to be re-named 40-60, such was the havoc it wreaked.
Zubkov, along with Slovakia and Austria failed to start their second runs, the shattered Austrian sled being dragged away looking like it had been in collision with a freight train. Japan crashed at the 13th corner in the second run.