Khachanov, 22 and bidding to make the last 16 of a Slam for the third time this year, took the opener while Nadal, who converted just one of five break points in the set, needed strapping to support his right knee in the changeover
New York: World number one and defending champion Rafael Nadal came back from a set and break down to defeat big-hitting Karen Khachanov 5-7, 7-5, 7-6 (9/7), 7-6 (7/3) and reach the US Open fourth round.
The top seeded Spaniard triumphed after an epic four hour 23 minute struggle on Arthur Ashe Stadium in a match where the 22-year-old Khachanov had served for a two sets to love lead in the 10th game of the second set and had a set point in the fourth-set tiebreaker on Friday.
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Nadal, seeking a fourth US Open title and 18th major, will face Georgia's world number 37 Nikoloz Basilashvili for a place in the quarter-finals.
Basilashvili reached the last-16 of a Slam for the first time by seeing off Argentina's Guido Pella 6-3, 6-4, 1-6, 7-6 (7/4).
"Karen played well. He's improving always. He's young. He has everything. I really see him winning a lot of matches in his career," said Nadal who has now reached the fourth round in New York for the 10th time.
"For me personally, it was a physical, demanding match. It was mentally demanding."
Khachanov, 22 and bidding to make the last 16 of a Slam for the third time this year, took the opener while Nadal, who converted just one of five break points in the set, needed strapping to support his right knee in the changeover.
"I am going to be at 100% for the next match," explained Nadal.
The top seed was quickly down 3-1 in the second set before battling back to 4-4. Khachanov cracked when serving for a two sets lead in the 10th game.
Nadal took advantage with a love service hold and a break to level the contest just moments after the roof was closed.
A thrilling tie-break settled the third set with Nadal clinching it after a lung-busting 39-shot rally on a fifth set point.
But the drama wasn't over as Nadal was broken in the 10th game of the fourth set as he served for the match He then had to save a set point in the 12th game before cruising through the tiebreaker to claim his 25th win against just one loss since capturing an 11th Roland Garros title in June.
"I gave everything I had. Just a few points difference and it could go another way. Big respect to Rafa. That's why he's No. 1, such a great fighter," said Khachanov.
South Africa's Kevin Anderson, who was runner-up to Nadal last year, outlasted Canadian teenager Denis Shapovalov 4-6, 6-3, 6-4, 4-6, 6-4 as the roof on the new Louis Armstrong Stadium was closed for the first time.
"Felt like being in a coliseum. Constant noise going on the whole time," said Anderson after his second five-setter in three rounds.
The fifth seed, runner-up to Novak Djokovic at Wimbledon, next faces ninth-seeded Austrian Dominic Thiem, who made the last 16 for the fourth time in five years with a 3-6, 6-3, 7-6 (7/5), 6-4 victory over American Taylor Fritz.
Thiem has now put together three wins in a row for the first time since finishing runner-up to Nadal at Roland Garros.
John Isner, the last American man standing, fired 34 aces, 85 winners and saved the three break points he faced in beating Serbia's Dusan Lajovic 7-6 (10/8), 6-7 (6/8), 6-3, 7-5.
He will face Milos Raonic who put out 2016 champion Stan Wawrinka 7-6 (8/6), 6-4, 6-3.
Croatian 20th seed Borna Coric made the last 16 of a Slam for the first time with a 6-3, 7-5, 6-2 victory over Russia's Daniil Medvedev.
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