Novak Djokovic reached an eighth successive US Open semi-final, downing Andy Murray 7-6 (7/1), 6-7 (1/7), 6-2, 6-4 to set up a clash against Kei Nishikori for a place in the title match.
World number one Djokovic, the 2011 champion, clinched his 50th win in New York and 13th in 21 meetings against his childhood rival who had taken the 2012 title.
Nishikori, the 10th seed, had earlier needed more than four hours to defeat third seed Stan Wawrinka 3-6, 7-5, 7-6 (9/7), 6-7 (5/7), 6-4 to become the first Japanese man in the semi-finals in 96 years.
Wimbledon champion Djokovic and Murray had spent a record-equalling 4 hours 54 minutes contesting the 2012 final and their quarter-final clash threatened to surpass that mark when they needed over two hours to get through the first two sets of a tie that started on Wednesday and finished Thursday.
By the end, however, Murray was struggling with what appeared to be a recurrence of his long-standing back problem, a legacy of having spent three and a half hours more on court than Djokovic in getting to this stage.
But victory was also a testament to the top seed's intimidating defensive skills as he saved 12 of 16 break points in the 3-hour 32-minute encounter which saw Murray commit 65 unforced errors to Djokovic's 48.
"We both gave our best and at times the tennis was not nice but that was due to the intense physical battle in the first two sets," said Djokovic.
"I didn't expect anything less from Andy. Our last few matches have been three and four hours and he has a lot of quality on all sorts of surfaces.
"I knew it would be a tough match and that the more aggressive player would win."
Djokovic and Nishikori are 1-1 in career meetings but their last clash was three years ago.
"It's great for Kei and Japan for him to be in the semi-final. He serves and moves very well," said the world number one who has made the final in New York in the last four years.
In a breathtaking first set of big-hitting, fine angles and lung-busting sprints, the two opening games were breaks, taking 13 minutes to complete.
Djokovic raced into a 4-1 lead but Murray pulled it back to 4-4 while the ninth game featured a 29-shot rally and the 10th a 104mph forehand off the Murray racquet.
But it was the world number one who played the more composed tiebreak, helped by a third Murray double fault and a rare loose backhand volley as Djokovic nosed in front after 73 minutes.
Djokovic was 3-1 up in the second set before Murray clawed his way back to 3-3. They exchanged breaks again to 4-4 with the Serb picking up a time violation before saving a set point in the 11th game.
Murray, however, swept through the tiebreak to level the tie as the clock nudged midnight and Djokovic dropped his first set of the tournament.
For the third set in succession, Djokovic grabbed the early break at 3-1 and this time held on, even piling on the agony with another break of a suddenly lacklustre Murray to claim the set 6-2.
Clearly struggling physically, Murray cracked in the 10th game of the fourth set with the match over when he netted a backhand.