Isner fired 18 aces, saved both break points he faced and broke Lacko three times on the way to victory, his fourth in four career meetings with Lacko.
"It was a good win," Isner said. "I think I'm getting more comfortable on this surface, especially with the positioning on my return... I was challenging him on a lot of return games. I was very happy how I came through that."
Isner next faces eighth-seeded Adrian Mannarino of France, who beat Uzbekistan's Denis Istomin 6-2, 7-6 (7/3).
British qualifier Daniel Evans, who ousted defending champion Frances Tiafoe in the first round, reached his third tour level quarter-final with a 6-0, 6-2 victory over South African Lloyd Harris.
Evans next faces sixth-seeded Italian Andreas Seppi, a 6-3, 4-6, 6-1 winner over Australian Jordan Thompson.
Top-seeded Juan Martin del Potro will fight for a quarter-final berth against American Reilly Opelka on Thursday.
Argentina's del Potro won his first match of 2019 when he beat Japan's Yoshihito Nishioka in the first round and is looking to continue his comeback from the broken right knee cap that kept him out of the Australian Open.
"I need to keep working hard on my legs because I felt tired at the end of the second set, but that's normal for (right now)," said del Potro, who hadn't played since hobbling out of the Shanghai Masters in October.
Opelka is coming off a maiden ATP tour title at the New York Open, where he rained 43 aces on Brayden Schnur of Canada in the final on Sunday.
First Published: February 21, 2019, 12:26 PM IST