The Scotsman was never in any danger of losing his match against Argentine baseliner Leonardo Mayer but did drop a set for the first time in the tournament.
If there were any heart flutters amongst his army of supporters, who were queued up outside Louis Armstrong Stadium to catch a glimpse of the 26-year-old, they were short-lived as he instantly regrouped and ran away with the fourth set to win 7-5 6-1 3-6 6-1.
"It was a very tough match," said the defending champion, whose next opponent is Germany's Florian Mayer. "Both of us did a lot of running.
"I started to move better as the match went on. He's a big hitter of the ball and I had to defend a lot."
The queues were even longer at court 17 where Martina Hingis was making her comeback to grand slam tennis.
The former world number one was granted a wildcard entry to the doubles with Daniel Hantuchova but the pair fell at the first, losing 6-3 7-5 to defending champions Sara Errani and Roberta Vinci.
For Hingis, who retired for a second time in 2007, it was a return to forget as she finished with back-to-back double faults to close out the match.
Novak Djokovic kept his perfect record intact after surviving an early test from Germany's Benjamin Becker on a baking hot day at Flushing Meadows, where gusting winds provided little relief from the heat and made it hard for the players to hit cleanly.
The world number one saved two set points in the opening set before rebounding to win 7-6 (2) 6-2 6-2 and advance to the next round against Portugal's Joao Sousa, a five-set winner over Jarkki Nieminen of Finland.
"It was a struggle," Djokovic said. "It was a lot of unforced errors, very windy conditions.
"You couldn't really read and kind of predict where the ball is going to go, so you have to be very alert."
Tomas Berdych, the men's fifth seed and a semi-finalist last year, beat American Denis Kudla 7-6 (3) 7-6 (3) 6-3 and will face Frenchman Julien Benneteau in the next round.
China's Li Na became the first player to reach the round of 16 when she defeated British teenager Laura Robson 6-2 7-5.
Li fired down 11 aces and needed just 81 minutes to avenge her third round loss to Robson at Flushing Meadows last year.
"I was a little bit surprised because today I have a lot of aces. It was like, wow," said Li, who plays Serbia's Jelena Jankovic next.
Robson contributed to her own downfall by committing 30 unforced errors, 15 in each set, but said she was happy with her steady progress in the game.
"I think I'm going in the right direction. I feel like I'm improving and working on a more all‑around game," she said.
"It's going to take a lot of hard work, but I'm willing to do that."
The ultra-consistent Agnieszka Radwanska wore down Russia's Anastasia Pavlyuchenkova 6-4 7-6 (1) to also reach the fourth round, continuing her impressive streak at this year's grand slams.
If she wins her next match, the third-seeded Pole will become the only woman to reach the last eight at all four grand slams this year.
"Well, of course I will do everything to make the quarter-final this year," she said. "I like the hard court and I really had great results on that surface. I think it's just something wrong here that I can't pass the fourth round.
Sloane Stephens beat Jamie Hampton 6-1 6-3 in a battle between two of America's brightest prospects to set up a possible showdown with Serena Williams, if the defending champion wins her night-time clash with Yaroslava Shvedova.
"I think I'm a great competitor. I've come out of a lot of tough situations, a lot of ugly ones," Stephen said.
"That's what I've worked on a lot this year: staying in matches, being able to fight, really digging deep. I think that's helped me a lot this year."