The storied venue outside Pittsburgh hosts a record ninth U.S. Open, and provides a brutal backdrop for the year's second major.
Oakmont Country Club is often called the "hardest" course in golf, and the tournament will be packed with compelling storylines.
Phil Mickelson, who will turn 46 on Thursday's opening round, is vying to finally win a U.S. Open after a record six runner-up spots. Victory would complete the career grand slam of all four major titles, and make him the oldest champion ahead of 45-year-old Hale Irwin, but the veteran left hander has not won since the 2013 British Open.
The world's top three players -- Jason Day, Jordan Spieth and Rory McIlroy -- resume their battle for supremacy, all hoping to add to their major hauls and enhance their status in the history of the game.
Can surprise Masters champion Danny Willett
prove he is not a one-major wonder, or will another unsung player step into the limelight?
Will Oakmont live up to its roguish reputation?
"It's probably the hardest course in the world on any given day without messing with the set up," Australian Geoff Ogilvy, the 2006 champion, told CNN's Living Golf.
The U.S. Open is often seen as the toughest of golf's four majors to win, with tight fairways, thick rough, slick greens and punishing pin placements. Par is considered a good score.
'No train wrecks'
Tournament organizer Mike Davis, executive director of the USGA, says the aim at a U.S. Open is to create the "most complete test of golf."
"They are going to test your shot-making abilities, your strategic and course-managing skills and they are going to test your nerves, too," Davis told Living Golf.
Ogilvy, who handed Mickelson arguably his most devastating U.S. Open defeat 10 years ago, added: "U.S. Opens really are kind of damage-control tournaments -- making a four instead of five, making a five instead of a six. Not having train wrecks."
Oakmont, which opened in 1903, is a wide open expanse of former farmland featuring no water and almost no trees.
The difficulty lies in severe bunkering -- including the infamous "Church Pews" row of bunkers on the third and fourth holes -- and hugely undulating greens, "which make Augusta's look flat and easy to putt," according to Ogilvy.
"I really think it is the hardest golf course we've ever played," Mickelson told reporters in Memphis last week.
"A lot of golf courses, when it challenges you tee to green the way Oakmont does, it usually has a little bit of a reprieve on the greens, and you really don't at Oakmont."
Australia's Day heads into the week looking to cement his status as world No. 1 and add to his 2015 U.S. PGA title, while Spieth is the defending champion after triumphing at the controversial Chambers Bay last year.
The 21-year-old Spieth, who had just won the Masters for his maiden major, became the youngest U.S. Open winner in 92 years when he profited from Dustin Johnson's three-putt on the final hole 12 months ago.
But the Texan will have his own baggage to contend with at Oakmont after blowing a five-shot lead with nine holes to play in his defense at Augusta in April.
Spieth even had to endure a heckler shouting "Remember the Masters"
as he clinched a PGA Tour win in the Lone Star state last month.
Like fellow 20-somethings Day and Spieth, Northern Ireland's world No. 3 McIlroy is also in form with a recent victory to his name as he looks to add a fifth major title and first since the 2014 U.S. PGA.
McIlroy won the U.S Open at a rain-softened Congressional in 2011, two months after his own Masters collapse when he squandered a four-shot lead heading into the last day.
This week's tournament will be without Tiger Woods after the former world No. 1 announced he has not recovered sufficiently from multiple back surgeries.
The 40-year-old, who won the last of his 14 majors at the 2008 U.S. Open at Torrey Pines in California, has not played since last August.
One man who unlocked Oakmont's secret was Johnny Miller, who charged to victory with a final-round 63 -- the joint lowest score ever in a major -- in 1973.
Other notable stagings at Oakmont include the legendary Ben Hogan's fourth major title in 1953 during a still unmatched run of victories in that year's Masters, U.S. Open and British Open.
Oakmont is also where a 22-year-old Jack Nicklaus served notice of his future greatness by clinching the first of his record 18 major titles.
The rookie from Ohio defied the taunts of "Fat Jack" from the massed fans of local hero Arnold Palmer to beat the reigning Masters champion in an 18-hole playoff.
"Now that the big guy is out of the cage, everybody better run for cover," Palmer, then a five-time major champion, said afterwards.
At the other end of the major-winning scale, this week will feature a 52-year-old U.S. Open debutant.
Texan Wes Short Jr. has finally qualified for his first U.S. Open, having first tried as a teenager in 1982.
His only other major appearance is at the 2006 U.S. PGA Championship, where he missed the halfway cut.