John Isner started his pursuit of a fourth Hall of Fame Tennis Championships title with a three-set win over Kamil Majchrzak in the last 16.

Top seed Isner reached the quarter-finals after outlasting his Polish opponent 6-4 6-7 (5-7) 6-3 on the grass at Newport on Wednesday.

Winner of the ATP 250 tournament in 2011, 2012 and 2017, Isner hit 25 aces and saved all five break points he faced.

"It wasn't easy, I played a long match, two hours and eight minutes. The conditions were brutal. It's windy and like 90 per cent humidity, so it was tough conditions out there," Isner said. "But I'm happy to claw through there because it wasn't pretty at times, that's for sure."

The chase for a fourth at the #HallofFameOpen has begun for @JohnIsner @TennisHalloFame | #ATP
— ATP Tour (@ATP_Tour) July 18, 2019

Next up for Isner is Matthew Ebden in a rematch of the 2017 final after the Australian defeated Denis Kudla 6-2 6-2.

While Isner progressed, seeds Adrian Mannarino and Jordan Thompson exited in the round of 16.

French second seed Mannarino was beaten by Tennys Sandgren 6-4 6-1, while third seed Thompson lost 6-2 7-6 (8-6) to Marcel Granollers.

Alexander Bublik knows it's #HotDogDay #HallofFameOpen pic.twitter.com/lLUGjjHFhi
— Tennis TV (@TennisTV) July 17, 2019

It was not all bad news for the seeds as Ugo Humbert (fourth) and Alexander Bublik (seventh) advanced at the expense of Ramkumar Ramanathan and Viktor Troicki respectively.

Elsewhere, Mischa Zverev saw off Guido Andreozzi 6-4 6-4 and Christopher Eubanks lost 6-4 6-3 against Ilya Ivashka.