The luck of the draw dropped Federer into in the same top half as Nadal, putting a damper on what could have been. To add insult to injury, on Saturday No. 2 seed Andy Murray pulled out of the tournament with a nagging hip injury. The No. 2 seed's slot has been taken by No. 5 Marin Cilic.
Nadal and Federer have never worked out their differences at this tournament at any stage, and both will have to do some heavy lifting if they hope to iron out that quirk in their history. They launch their US Open campaigns Tuesday, with Nadal on display during the day session and Federer once again headlining the night.
Nadal plays a Novak Djokovic disciple, Dusan Lajovic. In their only previous meeting, Nadal dusted Lajovic with straight-sets ease in the fourth round of the 2014 French Open, the year Lajovic rose to his career-best ranking of No. 57. But he's since dropped back to No. 85. Lajovic, 27, wrings the most out of a game that is solid but unspectacular. He has no great weapon, which raises the question: How do you beat Nadal without one?
Federer takes on Frances Tiafoe, 19, who is generally thought to have the most upside among the promising cohort of young Americans. Tiafoe is an explosive athlete, as he demonstrated in his second-round meeting with Federer at the Miami Masters earlier this year. The first set was close, but Federer ultimately won 7-6 (2), 6-3. Just weeks ago in Cincinnati, Tiafoe logged an impressive win over 20-year-old sensation Alexander Zverev, who is the No. 4 seed here.
Here are two other themes that will be in play Tuesday:
U.S. women on full display
All Grand Slams tend to load up the wild-card queue with native talent, but even without that in play, the US women who will see action Tuesday constitute an impressive fleet of 14 players. Four of the five U.S. women who snagged wild cards are on the schedule, led by former junior No. 1 Kayla Day.
The heartening detail for U.S. fans: Only two of the U.S. women face seeded players, and one of them (Alison Riske) plays a fellow countrywoman, No. 20 seed CoCo Vandeweghe. Christina McHale will battle talented but inconsistent No. 19 seed Anastasia Pavlyuchenkova.
Madison Keys is seeded deceptively low, at No. 15. But she's on the short list of contenders and working back toward her career-high No. 7 ranking following nagging wrist and shoulder injuries. She'll meet a rising opponent in Elise Mertens, a 21-year-old Belgian who is at a career-high ranking of No. 47.
Which Kyrgios will we see?
Nick Kyrgios is seeded No. 14 and nicely positioned to make it to a potential fourth-round date with Federer. But will the 22-year-old Australian's body -- and mind -- hold up that long?
Kyrgios retired from three consecutive tournaments this year, including Wimbledon, with persistent hip pain. But he won two matches at the Montreal Masters, then stunned everyone -- including himself -- by slashing his way to the Cincinnati Masters final.
He told the media afterward: "Where I was three weeks ago, it wasn't good at all. Now I'm in a Masters final. That's a very Nick Kyrgios thing to do. I don't know. It's crazy."
Temperamentally, Kyrgios has had trouble with long-term focus at two-week events using a best-of-five Grand Slam format. He'll have a chance to challenge that criticism thanks to a soft draw. His first-round opponent is fellow Australian John Millman, 28, who has just two career wins over top-20 players. The most formidable player standing in Kyrgios' path to the fourth round is the clever but underpowered 33-year-old, No. 33 seed Philipp Kohlschreiber.
What? A No. 33 seed?
There is an explanation: Murray withdrew after the draw was made, and Cilic was promoted to take his place in the bottom of the draw. The brackets then shifted. Since the seedings couldn't be otherwise tampered with, an "extra" seeding spot was added to make up for the Murray's withdrawal. Kohlschreiber qualified for it because he would have been next to be seeded based on ranking when the draw was made.