The giant Isner, who famously featured in the longest match in tennis history when he beat Nicolas Mahut 70-68 in a fifth set at Wimbledon in 2010, saw his run in this year's tournament ended by a knee injury after just five minutes on court.
But two weeks on, the second seed powered through a first-set tie-break without dropping a point and broke twice in the second set to win 7-6 (7/0) 6-2 in an hour and 20 minutes against the world number 110.
Isner was the only home player to progress from today's four matches, as James Blake lost 6-4 5-7 6-1 to Frenchman Adrian Mannarino and Stefan Kozlov was also beaten in three sets.
The 15-year-old, who impressed in the boys' tournament at SW19, marked his first ATP Tour appearance by winning the second set in a lengthy tie-break against Michal Przysiezny of Poland but ultimately went down 6-3 6-7 (9-11) 6-4.
Yuichi Sugita of Japan beat Canada's Jesse Levine 7-5 7-5 in the day's other match.