The 43-year-old finished three-under-par and the only man in red figures, three shots clear of Sweden's Henrik Stenson with overnight leader Lee Westwood a shot further back alongside compatriot Ian Poulter and Masters champion Adam Scott.

"Phil's round was incredible," 18-time Major winner Nicklaus wrote on his official Twitter account. "After his bad break on 16 (where his tee shot rolled back off the green), to then get up and down showed a lot of guts. And the two great shots at 17 (to set up a birdie) ended the tournament.

"I want to offer my sincere congratulations on a championship well played."

Mickelson, who became the third successive Open champion over the age of 40 after Darren Clarke and Ernie Els, had recorded just two top-10 finishes in his previous 19 Open appearances.

But the left-hander had warmed up for Muirfield with a first individual victory in Britain the week before on the links of Castle Stuart in the Scottish Open, preparation which clearly paid off as he came from five behind on the final day.

"This is just a day and a moment that I will cherish forever," Mickelson said.

"This is a really special time and as fulfilling a career accomplishment as I could ever imagine "It's probably the greatest and most difficult win of my career. It is great to be part of any Open Championship and to win at Muirfield feels amazing.

"I did enjoy links golf when I first played at the Walker Cup in 1991 at Portmarnock. It was a wonderful test but the conditions and the penalty for missed shots in the Open Championship are much more severe than we played then and it took me a while to figure it out I would say.

"It's been the last eight or nine years I've started playing it more effectively, I've started to hit the shots more effectively. But even then it's so different than what I grew up playing.

"I always wondered if I would develop the skills needed to win this championship. This has been the biggest challenge for me to overcome and capture this championship, this trophy."

Mickelson's win lifted him to second in the world rankings for the first time since September 2010, albeit four points behind number one Tiger Woods.

Woods started the final round just two off the lead but was never a factor after dropping three shots in his first six holes, two of them coming when he three-putted from long range.

"I didn't really play that poorly," said Woods, whose quest for a 15th major title - and first since 2008 - will continue at next month's USPGA Championship. "I just couldn't ever get the pace of the greens - they were much slower.

"I've won 14 majors and, in that spell where I haven't won since Torrey Pines, I've been in there. I've been in probably about half the majors on the back nine on Sunday with a chance to win during that stretch. I just haven't done it yet. And hopefully it will be in a few weeks."