Rafael Nadal (No. 1 seed)
The 31-year-old Spaniard has re-ascended to No. 1 in the world after compiling a 49-9 record in 2017 with four titles, including his 10th French Open crown and 15th Grand Slam title in June.
Nadal is seeking his third US Open title after winning in 2010 and 2013 but could have to go through his arch-rival Roger Federer in the semifinals. The two have never played in the US Open.
"Being No. 1 after all the things that I have been going through the last couple of years is something unbelievable," Nadal said. "So (it) is, for me, an amazing achievement to be back to that position after three years."
Roger Federer (No. 3 seed)
Federer is playing some of the best tennis of his historic career at the ripe old age of 36. The Swiss Maestro is 35-3 in 2017 with five titles, including his 18th and 19th Grand Slam titles at the Australian Open and Wimbledon.
He pulled out of the recent US Open warm-up in Cincinnati with back trouble but will have had almost two full weeks of rest as he ramps up to challenge for his sixth US Open crown and first since 2008. He opens against American upstart Frances Tiafoe.
Alexander Zverev (No. 4 seed)
The 20-year-old German is up to a career-high No. 6 in the world. His five titles in 2017 include back-to-back outdoor hardcourt crowns in Washington, D.C., and Montreal, the latter featuring a straight-sets win over Federer in the final.
Marin Cilic (No. 5 seed)
The 2014 US Open champ is always a threat on hardcourts. His summer has included a run to the Wimbledon final, where he lost to Federer in straight sets.
Grigor Dimitrov (No. 7 seed)
Nicknamed "Baby Fed," Dimitrov appears poised for a deep run in Flushing Meadows. He's coming off winning the title in Cincinnati, where he beat Juan Martin Del Potro, John Isner and Nick Kyrgios en route to the title.
Karolina Plíšková (No. 1 seed)
With Serena Williams expecting her first child and out of the US Open, the women's field remains more or less wide open. Still, the world No. 1 reached the finals of the 2016 US Open, losing to Angelique Kerber. This year's she's advanced to the quarters at the Australian Open, the semis at the French Open and the second round at Wimbledon.
Garbiñe Muguruza (No. 3 seed)
Muguruza may be the hottest player on tour, having won Wimbledon over Venus Williams in the final and then powering her way to her second title of the season in Cincinnati with a commanding 6-1, 6-0 victory over No. 2 seed Simona Halep.
Simona Halep (No. 2 seed)
The Romanian has never won a Grand Slam title and got a brutal draw with 2006 champ Maria Sharapova in the first round.
Angelique Kerber (No. 6 seed)
Last year's champion is down to No. 6 in the world and hasn't won a title in 2017.
Venus Williams (No. 9 seed)
At 37, she's playing some of her best tennis, reaching the finals of the Australian Open and Wimbledon.
Follow Adam Zagoria on Twitter @AdamZagoria for updates throughout the U.S. Open.