Isner played superb tennis in the third and fourth sets but Murray held on and proved the stronger in the tie-break to set up a last-four clash with either Nadal or Andy Roddick.

The British number one had beaten Isner, who stands 6ft 9in tall, in straight sets in their only previous grand slam meeting at the Australian Open last year but there was no doubt he was a danger having won nine matches in a row before today.

It was tense stuff early on, the pair testing each other out in front of a sparse crowd on Arthur Ashe Stadium, but in the 11th game Murray’s chance came, a double fault giving him his first two break points, and he took the first when Isner miscued a forehand.

The feeling was the longer the match went on the more it would favour Murray, so losing the first set was a major blow to Isner, who had sweated so much against Gilles Simon yesterday he had had to send a friend to the Nike store for extra shirts.

The conditions were back to those of first week, the sun beating down on Arthur Ashe, and Isner’s task got a lot harder when he was broken to love at the start of the second set.

The pressure of the opener lifted, the Scot was now playing superbly and two more glorious passes gave him points for a 3-0 lead but this time Isner’s serve came to his rescue.

The American lifted his game again but it was not enough to deny Murray the second set.

Isner’s hopes looked extremely faint now but he hit back at the start of the third with his first break of the match, taking his third chance with a return that was too hot for Murray to handle.

Murray had his chance in the fifth game when he created a break point with a backhand lob winner after somehow reaching a drop shot, but he could not take it, sending a backhand just long and swearing loudly.

Isner was rock solid on serve now and he clinched the set with his 13th ace.

The American received treatment for an ankle problem before the start of the fourth set and he continued his policy of all-out attack, piling the pressure on Murray.

Doubting the American’s staying power – given his history-making Wimbledon performance – would, of course, be foolish and Murray was having an almost constant conversation with himself as he sought the breakthrough.

But Isner was playing very well now, and it was the home favourite, being roared on by a much fuller stadium, who created break points, two of them, in game nine.

Murray came up with an ace on the first and on the second he scrambled a half-volley winner after a second serve Isner thought was out. The 26-year-old did not challenge, and replays showed the ball to be a fraction in.

It was a huge moment, but if Murray’s luck was in there it definitely was not on the second point of the 12th game when, with Isner serving at 0-15, a shot from the Scot was called out and over-ruled just as his opponent put a backhand long.

Murray hung his head and into a tie-break they went. Isner had won all six at this tournament and 11 in a row in total, but a double fault handed the advantage to his opponent.

A missed volley gave the fourth seed two serves for victory, and he made no mistake, sealing it when Isner fired a forehand return wide after three hours and 24 minutes.