Canadian rookie Rob Cooke, who hails from Whitehorse, Yukon Territory, was the first musher to leave Fairbanks as fans looked on from the starting gate and along the expressway.
The Iditarod Trail Sled Dog Race usually kicks off 362 km south in Willow. But because of a lack of snow this year, officials shifted the entire route around the Alaska Range and an area that left many mushers bruised and bloodied last year.
This is only the second time Fairbanks has hosted the official start; similar low-snow conditions moved the Iditarod there in 2003.
The finish line remains in Nome, on the state's wind-whipped western coast.
The route change eliminates mountainous terrain and a treacherous gorge. But the race now will be run on about 965 km of river ice, and that can create a whole new set of obstacles.
Some mushers have hinted the new path might benefit Pete Kaiser, a young musher who recently won an all-river ice sled dog race in southwest Alaska. Kaiser disputed that Monday.
"I don't see it as an advantage or disadvantage for me or anyone else, really," he said as he took a break from packing his sled before the race started.
"It's just another trail through the state, and it's still a thousand miles, and it's still through some rugged country," Kaiser said.
Lance Mackey is running the race with a young dog team and is handling the changes in stride.
The four-time champion said the fact that most of the thousand or so dogs participating in the race have never seen this part of Alaska is "kind of cool."
"Not a dog in this yard has been on this trail or this race," Mackey said. "Everybody's on the same playing field in that aspect."
The new route reduces the number of checkpoints in the early part of the race, but it adds stops at villages that have never been part of the Iditarod — like tiny Huslia, an Athabascan village of about 300 residents.
Alaska's fairly warm and snowless winter was caused by the same weather pattern that repeatedly dumped snow on the East Coast. It has made for poor conditions south of the Alaska Range, especially in the area of the Dalzell Gorge, considered the roughest patch for mushers and dogs.
This is where many mushers were injured in crashes last year. Officials said this year's conditions there are worse.
Four-time champion Martin Buser said the lack of snow in the greater Anchorage area made for a challenging training season.
Buser said he intends to slow his start this year after setting a blistering pace in the early part of last year's race and then fading back.
"Yeah, I'll go slower this year, try not to be first at the halfway but try to be first at the finish," he said.
The 2015 Iditarod features 78 mushers, including 20 rookies and six former champions.
Unlike the festive ceremonial start, which is designed to let fans interact with mushers, the staggered start in Fairbanks is all business for participants.
Racers leave the starting chute in two-minute intervals. The first musher to reach the finish line will pocket $70,000, which is $19,600 more than what defending champion Dallas Seavey received last year because of an increased purse.