Fourth seed Karlovic, who served 17 aces to remain unbroken for the tournament, earned a Saturday semi-final clash with fifth-seeded Frenchman Adrian Mannarino, who beat Lu Yen-hsun of Taiwan 3-6 6-1 6-1.
Karlovic and Mannarino are the highest remaining seeds in the tournament, following the elimination of third seed Alexandr Dolgopolov, beaten 2-6 6-3 6-4 by unseeded American Donald Young in a match that stretched nearly two hours.
"It was really cold and it wasn't easy to move and be aggressive but in the beginning, I was playing really good. It might be one of my best sets," Karlovic told the tournament website.
"Everything that I hit was in. I was confident in my game."
In the first evening match, Mannarino also took a while to warm up but dominated once he had as Lu struggled on serve in the final two sets.
"In the beginning it was tough to get my rhythm," Mannarino said. "The wind was bearing down and it was really cold. Finally, in the second set, I tried just to focus on my legs and move better and try to be more consistent."
For the second time in as many weeks, Young's semi-final opponent will be Australian Bernard Tomic, who dispatched 19-year-old Japanese qualifier Yoshihito Nishioka 6-3 6-1.
Young edged Tomic in three sets in the Memphis Open last Saturday.
(Reporting by Andrew Both in Cary, North Carolina; Editing by John O'Brien)
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