South Africa's Anderson was no match for lucky loser Thiemo de Bakker, with the Dutchman progressing to the quarter-finals of the hard-court tournament courtesy of a 6-4 7-5 victory.
Anderson, ranked 17th, could only break the de Bakker serve once, with the world number 142 immediately breaking back in the second set before going on to seal the win in one hour 49 minutes.
De Bakker will face unseeded German Benjamin Becker in the last eight, after the latter upset Taipei's seventh seed Yen-Hsun Lu 6-4 6-3.
Isner, the world number 12, was playing his first match in his title defence, and was pushed all the way by two-time winner Robby Ginepri before saluting 4-6 7-6 (7-5) 7-5.
The big-serving American sent down 30 aces, and saved two match points in the 10th game of the third set, before breaking in the next game and serving out the contest to love.
Isner's next assignment is eighth-seeded Australian Marinko Matosevic, who dispatched with American Tim Smyczek 6-4 7-5 at the ATP 250 event.