Former world number one and 2018 Australian Open champion Wozniacki moved through to the Charleston final thanks to Saturday's 6-3 6-4 win over Petra Martic.
Wozniacki – the fifth seed – hit 21 winners to only 13 unforced errors as she reached her first final of the season and third in Charleston, where she was champion in 2011 and runner-up in 2009.
"It's been a long time since I made this long run here," said Wozniacki. "So I'm just really happy to be through to the finals once again, and I've been feeling great this week."
Standing in Wozniacki's way is 2015 finalist Keys, who fended off Monica Puig 6-4 6-0 in a rain-interrupted semi-final on the Charleston clay.
Meanwhile, Victoria Azarenka reached her first final since returning to the WTA Tour following the birth of her son in December 2016.
Two-time grand slam winner Azarenka outlasted top seed Angelique Kerber 6-4 4-6 6-1 in a thriller final-four showdown at the Monterrey Open on Saturday.
Not since March 2016 had Azarenka – plagued by off-court and fitness issues – featured in a singles final but the fifth seed changed that against Kerber.
"It's quite incredible. I'm very pleased with the way I played today. It was an important match to see how I could do under pressure against a top player," Azarenka said.
"I haven't won many of those in the last couple of years, so it's good that I was able to turn it around and pick up my level, so I'm happy about that."