Wozniacki, a U.S. Open finalist in 2009 and 2014 but unseeded this year after being sidelined for two months by an ankle injury, dominated from the start and wrapped up victory in a speedy 78 minutes on a sun-splashed Arthur Ashe Stadium court.
"I know that when I play my best I'm tough to beat and I just do my thing," said the 74th-ranked Wozniacki, who will next meet Latvian Anastasija Sevastova, a 6-4 7-5 winner Britain's Johanna Konta.
"I'm not surprised that I could make it this far because I always believe in myself and I always think that when I get on court I'll win the match.
"Everybody wants to beat you. No matter what my ranking is, I always feel like I'm a target."
Wozniacki, who completed the New York City marathon inside three hours, 30 minutes after her loss to Serena Williams in the 2014 final, is back in full stride, as she showed by chasing down every shot that an increasingly frustrated Keys conjured up.
After rallying from a set and a break down in her opening match and then coming back from 5-1 down in the third to beat Japan's Naomi Osaka, Keys could not find a way past the former world number one, who clinched the match on her first match point.
"It was nerves a little bit," admitted Keys. "I definitely felt like I got off to a bad start and then I felt like I was trying to catch up from there.
"I feel like the match just got away from me."
Twice a finalist and twice in the semi-finals at the season's final grand slam, New York is certainly Wozniacki's kind of town.
The 26-year-old Dane keeps an apartment in New York and calls the city home, sleeping in her own bed during the Flushing Meadows fortnight.
The comfort level has been clearly evident during the first four rounds with Wozniacki dropping just a single set, that coming in her opening match, on way to the last eight.
"It feels so much better," said Wozniacki about being able to go home at night. "My mom has cooked. She's staying with me this week, which is nice.
"She's cooked a couple of meals. She does my laundry, as well. It's nice to have mom around.
"It's nice just being able to sleep in your own bed.
"I think that's kind of recharged my batteries."
(Editing by Rex Gowar/Andrew Both)
