Isner took one hour and 49 minutes to book a Friday last-eight date with compatriot Donald Young, who advanced with a 7-6 (7/3), 6-3 triumph over American Reilly Opelka in the indoor hardcourt event.
Bosnian Damir Dzumhur upset Belgian seventh seed Steve Darcis 7-6 (7/2), 6-4 in another second-round match. He will face the winner of a late match between Americans Ryan Harrison and Sam Querrey in the quarterfinals.
In first-round matchups, Georgia's Nikoloz Basilashvili downed Australia's Jordan Thompson 6-3, 6-0 and Kazakhstan's Mikhail Kukushkin ousted German lucky loser Benjamin Becker 6-3, 6-4.
Kukushkin will next face Barbados qualifier Darian King while Basilashvili meets Croatian top seed Ivo Karlovic on Thursday.
