The third-seeded American will play Saturday against Luxembourg's Gilles Muller, who ended his six-year ATP semi-final drought with a straight-sets upset of second-seeded South African Kevin Anderson.
The 28-year-old Muller, who won his sixth career Challenger title last May on grass but has been beaten in the only two ATP-level finals he has played, fired 14 aces and mustered one break of serve en route to a 7-6 (7/3), 7-6 (7/3) victory over Anderson.
In the day's other two quarter-finals, top seed and defending champion Mardy Fish was to take on Indian eighth seed Somdev Devvarman while American teenager Ryan Harrison plays Rajeev Ram, who beat Lleyton Hewitt in the second round.
Isner, who starred at the University of Georgia, thrived in hot-house conditions.
"This court is perfect for me. It's hot but the ball is moving pretty well, that's good for my serve," he said.
Isner secured two breaks per set to defeat Lu in 54 minutes on his second match point.
He saved an early break point but was never again threatened.
"I've been serving well," said the player who managed 30 aces in the previous round. "When I've had a chance, I've converted it."
Isner said his confidence has been boosted by the grasscourt title he won in Newport the week after Wimbledon.
"I feel like I have my swagger back, it's all about confidence now," said last year's Wimbledon marathon man. "I'm playing well."
Muller was pleased to make a breakthrough after more than two and a half years of toiling on the lower-level Challenger circuit as he tries to improve his 82nd ranking.
He is competing in just his third ATP tournament of 2011 after coming back from a knee injury and falling from the Top 100 in recent seasons.
He last made an ATP semi-final at Los Angeles in 2005.
"This feels good after playing for so long at Challengers," said Muller, who twice saved double break points against his serve.
"It was tough serving, with the sun in your face from one side of the court.
"I had to change my toss, but I got some aces on break points and that helped. This week is important for the confidence. When you save break points you know you can also win.
"I know I can beat a lot of top players when I play well. The problem has always been consistency. Now that I'm in the semis, I hope I can play even better."
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