The winner will likely face David Goffin, the Belgian No 9 seed, although he is still on the injury comeback trail and will not find a clash with Andrey Rublev a formality by any stretch of the imagination.
Should Nadal make it past the Ukrainian, as he has in six of their eight senior meetings, he will remain on course for a semi-final match against Roger Federer.
The Swiss will take on Philip Kohlschreiber in the night session on Arthur Ashe for his place in the quarter-finals.
Follow all the latest action from Nadal v Dolgopolov right here as it happens.
Rafael Nadal v Alexandr Dolgopolov LIVE
RAFAEL NADAL WINS SECOND SET 6-4
Ruthless efficiency from the world No 1 who quickly brings up three set points and serves an ace to ensure he only needs one.
6.45pm: Everything was starting to look rosy for Dolgopolov but all of a sudden, Nadal forces a break point and his power is too much. He breaks at the most crucial time and will serve for the second set.
Nadal leads 5-4, second set and one set to love
6.30pm: Dolgopolov manages to hold in a tight opening service game before Nadal holds to 15.
But the Ukrainian puts it right back into Nadal’s court with a love hold.
Neither player is making much of an impact on the other so far in the second set and we’re still on serve.
Dolgopolov leads 3-2, second set – Nadal leads by one set to love
RAFAEL NADAL WINS THE FIRST SET 6-2
This is comfortably the best Nadal has looked in the first set of any match at the US Open 2017. A comfortable hold seals the first set to muted applause from a half-full Arthur Ashe, many of whom probably weren’t expecting the world No 1 to be out on court so soon.
6.05pm: And now Nadal will serve for the set. A stunning cross-court backhand after chasing down an angular forehand seals the double break.
Nadal leads 5-2, first set
6pm: Dolgopolov eventually forces break-back point in game six after a Nadal double-fault, but the Spaniard responds brilliantly, firing inside-out forehands galore into far corner to make the save. There are two more opportunities but Dolgopolov can’t capitalise. Tough to turn down those chances against Nadal.
Nadal leads 4-2, first set
5.45pm: NADAL BREAKS! Given how poorly the world No 1 has started in his previous three matches, this is a surprise.
Dolgopolov squanders a 0-30, double-faults at 30-30 and then leaks his forehand out to hand Nadal the break.
Nadal leads 2-1, first set
5.35pm: With the court half in shade, Dolgopolov to serve first from the sunny end…
5.25pm: Players are out on court with the Spaniard once again wearing hot pink and Dolgopolov in a fetching red and yellow number.
5.20pm: Nadal has been far from flawless so far at Flushing Meadows. He was a break down in the first set against Dusan Lajovic and dropped the first set against Taro Daniel and Leonardo Mayer – and former US Open champion Boris Becker reckons he is beatable.
“I thought Nadal’s match with Mayer was fascinating – it was typical Nadal, wearing the other guy down,” said Becker, who is working as a pundit for live and exclusive broadcasters Eurosport in New York.
“He looks good but I thought he looked good from the get-go and that’s the way he wins on hard courts; with the long rallies and making it a three or four hour contest.
“If you want to beat Rafa you’ve got to do it in under two hours or it’ll be difficult.”
5.07pm: Pliskova wins! Absolutely battered Brady, who to be fair is playing in her first ever US Open main draw. 6-1, 6-0 and Nadal will be imminent.
5pm: I’ll be honest, the tennis has caught me on the hop a little today. With all the long matches and rain delays, a swift opening tie was the last thing I was expecting.
But Karolina Pliskova is absolutely demolishing Jennifer Brady and after just 45 minutes, the Czech No 1 seed has won 11 of the 12 games on offer and is on the brink of the quarter-finals with minimal fuss.
When they are done, it will be Nadal O’Clock and we will take you every step of the way.