"I'm so happy to reach another semi-final in my favourite tournament that's very special to me", said Del Potro.
He was left awaiting the victor of Tuesday night's second quarter final between Rafael Nadal and Austria's Dominic Thiem to see who he will play on Friday.
Despite that, the 29-year-old was never broken in the 3 hour 31 minute match where Isner unleashed 26 aces but was undone by 52 unforced errors compared to Del Potro's 14.
Del Potro could not convert the sole break chance in the opening set with Isner making the most of a mini-break in the tiebreaker.
"I had a shower, lay on the table and I didn't want to come back again", laughed Del Potro.
'Beating John in these kind of matches is epic, we were both exhausted in the end, we both fought all the match and I survived with my serve at a couple of important moments, ' said Del Potro. We both were exhausted in the end, we both fought until the end and I think I survived with my serve.
This was the 93rd Grand Slam win for the last year's semi-finalist who did not lose a set prior to this match, saving all three break points he faced to keep the pressure on John who failed to endure it, losing 35% of the points in his games and suffering two breaks from 10 opportunities he gave to Juan Martin.
It was all about Juan Martin in set number two, dropping three points on serve and creating a break point in the second game that Isner repelled with another ace.
The Argentinian had only won three of his last seven meetings with Isner but gained the break he needed early in the second set and maintained his advantage. The American wasted two game points in the eighth game and del Potro sealed the deal with another break when his rival netted an easy forehand, roaring towards the last four just like 12 months ago and hoping to go at least a step further this time around.
Later Tuesday, Nadal continued his pursuit of a fourth title in NY against Thiem, the man he beat to clinch an 11th French Open in June.
As the intense heat at FLushing Meadows continued Del Potro and Isner exchanged big serves in what was at times a fairly attritional affair.
Victory will put him into a 29th semi-final at the majors.
Saturday morning, forecasters predicted the system would not form until it passed over Florida and entered the Gulf. Given Florence's remote location, the storm won't be near any areas of land through at least the weekend.
Kavanaugh's confirmation is complicated by the sheer number of emails that exist during his years in the White House . The Senate judiciary committee was notified of the decision to withhold documents on Friday.
Del Potro - the 2009 victor of the men's singles at Flushing Meadows - breezed past Borna Coric in the final match of the day. Serena, seeded 17th, routed Venus 6-1, 6-2 in matching the most-lopsided victory in the Williams sisters' series.
The initial image, announced through Rovell, has a close up of Kaepernick's face with the caption: "Believe in something . Colin Kaepernick is not on an National Football League roster, but he does have his own ad campaign, courtesy of Nike .
Kohlschreiber now meets 2014 runner-up Kei Nishikori, who got past No. 13 Diego Schwartzman 6-4, 6-4, 5-7, 6-1. Roger Federer created yet another magical moment late in the match yesterday during a win over Nick Krgios.
The news agency reported that the judge also instructed them to provide an accounting of how the money has been spent . The twosome appeared on the Megyn Kelly Today show, where D'Amico claimed Bobbitt squandered $25,000 within 13 days.
Amazon has become the second publicly traded company to be worth US$1 trillion (NZ$1.52 trillion), hot on the heels of Apple . Amazon has briefly become the second US-listed firm to have a market value of more than $1 trillion (£779bn).
Kaia Kanepi of Estonia congratulates Serena Williams at the net after their match during the seventh day of the US Open. But having taken her first set against Williams in five career meetings, there would not be a second.
John Millman Just Knocked Off Roger Federer At The US Open
The 13-times grand slam victor had made easy work of the opening set, breaking Sousa twice, the second time to close out the set. Kei Nishikori , runner-up in 2014, was also pleased to get through in three sets in blazing sunshine on Louis Armstrong Stadium.
McEnroe: Don't penalise umpire for Kyrgios pep talk
From the coach, to the physio to maybe even a counsellor, these are the people you hire to get the best out of you. De Minaur took the opening two sets, including a bagel in the second, before Tiafoe fought back to make it 2-1.
Zverev sails into third round at U.S. Open
That was the first career Grand Slam final for Keys, who was one of four American women in the semifinals a year ago at the U.S. Former world No. 1 Novak Djokovic will be back on Arthur Ashe in prime time, facing American Tennys Sandgren.
Tropical Storm Gordon drenches South Florida
The system was lashing Florida with tropical-storm-force winds and heavy rains Monday morning, according to the hurricane center. At the time, peak sustained winds were 45 miles per hour , but wind gusts were in the 50 mph-to-60 miles per hour range.
Is Steven Gerrard smart enough to outfox his old boss?
The victor came after 62 minutes when Olivier Ntcham swept home to find the net at the end of a swift counter attack. A fuming Gerrard told Sky Sports: 'It's definitely a foul. "I have seen it again five times and it is a foul".
African leaders trooping to Beijing for 2018 FOCAC summit
Ramaphosa was hosted by Jinping at the State House on Sunday and will on Monday co-chair a Forum on China-Africa Cooperation. Both leaders later addressed a press conference where illegal migration and other issues were discussed.