The 37-year-old throat cancer survivor from Fairbanks and 11 dogs crossed the finish line under Nome's burled arch at 2:46 a.m. ADT Wednesday.
He yelled "Yeah, baby!" as he drove his team down Nome's Front Street. Fans mobbed him along the final 10 blocks, slapping his hand.
"I'm not much to brag very often, but damn, I'm going to this time," he said of his consecutive victories. "I don't know exactly how to explain it. I'm just blessed with an incredible dog team."
His family greeted him at the finish line and he received congratulatory phone calls from his father, Dick Mackey, a former Iditarod champion, and Gov. Sarah Palin.
Palin told Mackey: "You're a hero, and truly an inspiration to all of us."
For much of the race Mackey tussled for the lead with four-time winner Jeff King of Denali Park, who was about an hour back. He also struggled with dogs stricken with diarrhea and slowed by unseasonably warm weather that marked much of the trail.
But they were in noticeably better health in White Mountain, where mushers are required to take an eight-hour break before heading up the icy Bering Sea coast for the 77-mile homestretch to Nome.
"They're starting to perform the way I know they can," Mackey said Tuesday before leaving the checkpoint. "I think that this crew knows where they're at all of a sudden and they know that it's about over."
Mackey's dogs also quarreled on the trail. He had to drop Hobo, a leader that was badly injured in an ongoing rivalry with Larry, another leader. Some of his dogs were coughing and one is in heat.
Wednesday's win was a repeat of Mackey's 2007 feat when he became the first musher to win back-to-back runs in the 1,000-mile Yukon Quest International Sled Dog Race and the Iditarod in the same year. Last month, he won his fourth straight Yukon Quest.
Mackey used many of the same dogs that ran the 2007 Iditarod and the Quest this year and last.
King, a 51-year-old musher from Denali Park, ran most of the trail with a full team of 16 dogs that continued to look remarkably fresh and alert as the race progressed.
King finally dropped two dogs Tuesday at the checkpoint in White Mountain.
Running an equally competitive race for third place were Ramey Smyth of Willow, Ken Anderson of Fairbanks, Martin Buser of Big Lake and Hans Gatt, a three-time Yukon Quest winner from Whitehorse, Yukon.
Twelve mushers have scratched since the start of the Iditarod and one has been withdrawn. The latest out of the race was 43-year-old Steve Madsen of Cougar, Wash., who scratched Tuesday in Galena, citing concern for the health of his 11-dog team. Eighty-two mushers remain on the trail. Two dogs have died in this year's race, including a 3-year-old female struck by a snowmobile.
Organizers this year introduced a new tracking system that let fans follow online the real-time progress of 20 top mushers. Officials hope to expand the system to all participants in future races. Mackey and King each carried one of the devices.
In its 36th running, the Iditarod commemorates a run by sled dogs in 1925 to deliver lifesaving diphtheria serum to Nome.
The modern-day Iditarod trail crosses frozen rivers, dense woods and two mountain ranges, then goes along the dangerous sea ice up the Bering Sea shore.
Mushers compete for a piece of an $875,000 purse, to be paid out among the top 30 finishers to reach Nome. Mackey gets $69,000 and a new truck worth $45,000 for winning.
Mackey said before the race started that the prize money is important so he doesn't have "to get a real job."