NEW YORK — Rejuvenated at age 32, Lleyton Hewitt was two points away from reaching the US Open quarterfinals for the first time since 2006.
A champion at Flushing Meadows a dozen years ago, Hewitt could not close out Tuesday’s five-setter against 21st-seeded Mikhail Youzhny in the fourth round.
‘‘It’s one of the hardest games to win — the last one,’’ Hewitt said.
Dropping the last five games of the back-and-forth, nearly four-hour match, a fading Hewitt lost to Youzhny, 6-3, 3-6, 6-7 (3-7), 6-4, 7-5.
How close was it? Hewitt won more total points, 146-145. Wearing his trademark backward-turned white baseball hat, he got within two points of winning at 5-2, then served for the match at 5-3.
‘‘I left it all out there,’’ he said. ‘‘There’s not a whole heap more I could have done.’’
At 2-2 in the fifth set, Hewitt tore some skin off his left elbow while diving to the court for a shot. After Youzhny won the point to get to 15-30 on Hewitt’s serve, play was halted for a medical timeout while a trainer treated the bloody scrape on the Australian’s arm.
Two-time major champion Hewitt had been 7-0 in fourth-round matches in New York, but he hadn’t even been that far in seven years.
A former No. 1-ranked player who is currently 66th after a series of foot and hip injuries, Hewitt last got to the quarterfinals of any Grand Slam tournament at Wimbledon in 2009.
Asked whether he could see himself still competing at the US Open in three or four years’ time, Hewitt shook his head and replied: ‘‘I don’t know, mate. No idea.’’
Youzhny’s best Grand Slam showings have come at Flushing Meadows, where he made the semifinals in 2006 and 2010 — and also lost in the first round each of the past two years.
The 31-year-old Russian will face No. 1 Novak Djokovic in the quarterfinals. Djokovic won 45 of 53 service points while eliminating 43d-ranked Marcel Granollers, 6-3, 6-0, 6-0, in a grand total of 79 minutes Tuesday.
‘‘First of all, I need to recover after this,’’ Youzhny said, adding that it will be ‘‘really tough to beat’’ Djokovic.
Every time it appeared one man or the other was pulling away, the other got right back into it. Hewitt trailed by a set and a break before going ahead 2-1. Then he grabbed 11 of the first 12 points to start the fourth, going up 3-0 and 4-1.
But Youzhny responded with a six-game run. In the fifth set, Youzhny broke in the first game by making a long sprint, then sliding wide of the doubles alley, for a backhand winner. Sticking to the pattern, Hewitt broke right back.
In 80-degree heat, two of 12 active men who have made it at least as far as the quarterfinals at all four major tennis tournaments appeared content to hang out at the baseline for lengthy exchanges. Points would last 10, 20, 30 strokes.
‘‘Obviously,’’ Hewitt said, ‘‘could have gone either way.’’
With Hewitt serving for the win at 5-3, Youzhny earned a break by stretching for a volley winner with both players up at the net. Hewitt then missed a backhand to make it 5-4. That was part of a stretch in which Youzhny took 12 of 13 points. When Hewitt pushed a forehand long to get broken again, Youzhny led 6-5, and there would be no more shifts.
Defending champion Andy Murray encountered some problems early against 65th-ranked Denis Istomin of Uzbekistan, but the third seed soon righted the ship and advanced to the quarters for the third straight year with a 6-7 (5-7), 6-1, 6-4, 6-4 decision.
Ahead 5-3 in the opening tiebreaker, Murray dropped four points in a row.
Serving for the second set at 5-1, Murray hit a volley-lob that Istomin tracked down and, back to the net, sent back with a between-the-legs shot. What should have been an easy tap-in winner became a flubbed volley, and Murray put his hand to his face.
But he wound up taking that game, and was on his way to improving to 30-2 over his last five Grand Slam tournaments.
Next for Murray is No. 9 Stanislas Wawrinka. A day after his Swiss Davis Cup teammate and friend, Roger Federer, lost, Wawrinka served 14 aces to reach the round of eight at the US Open for the second time by beating No. 5 Tomas Berdych, 3-6, 6-1, 7-6 (8-6), 6-2.
After dropping the first set, Wawrinka served five aces in each of the next two, including a 131-mph serve down the middle to close out the third-set tiebreaker.