The 31-year-old Anderson made the last-eight at Flushing Meadows for the second time with a 6-4, 6-3, 6-7 (4/7), 6-4 win over grizzled Italian Paolo Lorenzi.
But the victory out on the temporary Louis Armstrong stadium came at a cost.
The nail on the middle toe of his right foot came off during the three-hour battle of attrition with his 35-year-old opponent.
“A lot of stopping and starting, so the toenails take a bit of a beating,” said the Florida-based Johannesburg native, who said he didn’t feel the pain as the match concluded.
“That’s actually always interesting. You’re out there with so much adrenaline, you’re feeling fine. Now I can barely put a shoe on. It will be fine. Just tape it up and I’ll be good for tomorrow.”
Being in agony — even from a humble toenail — is nothing new for the 6ft 8in (2.03m) Anderson.
He suffered a crippling hip injury at the end of 2016 that forced him to miss the Australian Open.
His ranking — once as high as 10 — fell to 80, its lowest in seven years.
Anderson returned to the tour at Memphis in February but then injury struck again at the French Open when a left thigh problem forced a retirement in the fourth round against Marin Cilic.
A leg injury meant a withdrawal at Queen’s while right elbow pain sidelined him from Winston-Salem on the eve of the US Open.
However, he still enjoyed an impressive summer hardcourt season, finishing runner-up in Washington and making the quarter-finals of the Montreal Masters.
On both occasions, it took world number six Alexander Zverev to stop him.
“Yeah, it feels great,” said Anderson, who was also a quarter-finalist in New York in 2015.
“I feel like I’m playing really good tennis. My body is healthy. It was a pretty tough loss at the beginning of this year with a few injuries.”
Anderson’s service has been virtually unplayable at the US Open, going into Sunday’s match not having been broken in 43 service games.
Lorenzi managed to spoil the run of perfection by breaking twice but Anderson can still boast 62 service holds in 64 games.
He has also fired 70 aces, 18 of which came on Sunday, and has hit the third-fastest serve of the tournament of 137mph (220.4km/h).
“I think a while back if you were tall, you have to come in. I don’t know if you actually gave yourself a bit of a chance,” explained Anderson.
“Now you see some of the tall guys who cover the court very well.”
Anderson will face either 17th seed Sam Querrey of the United States or Mischa Zverev of Germany, seeded 23, for a place in the semi-finals.
Anderson trails Querrey 8-6 in career meetings but a win in Montreal avenged the fourth-round loss he suffered to the American over five sets at Wimbledon in July.
He won his only clash with serve-and-volleyer Zverev back in 2010.