Harrison didn't drop his serve in beating Isner 6-4, 6-4. Harrison lost 16 points in 10 games serving and saved the three break points Isner managed. Isner had 10 aces but Harrison posted a break in each set in advancing to the quarterfinals.
The Sydney draw lost two other seeds as No. 2-seeded Gilles Simon withdrew with a neck injury and sixth-seeded Radek Stepanek allowed Julien Benneteau to advance he retired due to a sprained intercostal muscle four points into their Wednesday match.
Ivo Klec was inserted into the draw to replace Simon but Jarkko Nieminen made his stay a short one, rolling past Klec 6-3, 6-1 in 46 minutes.
Third-seeded Andreas Seppi needed three sets to get to the quarterfinals, beating John Millman 6-2, 3-6, 6-3 and No. 8-seeded Marcel Granollers stopped Fabio Fognini 6-2, 7-6 (7-4). Seppi and Granollers are the only seeded players left in the tournament and they face off in the next round.