Toronto, Canada – By Greg Stutchbury
The 24-year-old Isner, who was knocked out at the quarter-final stage last year, overpowered the 16th ranked Robredo with 20 aces to run out a 7-6 3-6 6-4 winner.
A noticeably frustrated Robredo said that while he had broken Isner's booming serve three times, he still had trouble with a ball that was clocked moving at more than 220 kilometers per hour (137mph).
"I feel good. I'm not going to change much from the way I played or am feeling," Robredo said.
"I played great from the baseline, was returning great and only had a couple of mistakes with my serve. The rest is positive for me, even though I lost, but if you play a guy like John, it can happen."
Robredo's demise ensured that none of the top four seeds would be in the semi-finals on Friday.
Isner will now meet Spain's Albert Montanes in the semi-finals after the eighth seed beat Swiss qualifier Michael Lammer 6-3 6-3.
Isner said he doubted if the ease of the Spaniard's path would have any bearing on their match.
"He has a deceptively strong serve," Isner, who beat Montanes in Auckland last year, added. "He's also very fast and has some great groundstrokes... so it will be tough."
France's Arnaud Clement continued a strong run with a 6-2 7-5 victory over sixth-seeded Austrian Juergen Melzer and will meet 2008 champion Philipp Kohlschreiber, who beat France's Marc Gicquel 6-3 6-1 in the late match, in the final four.
(Editing by John O'Brien)