Roger Federer defeated Philipp Kohlschreiber for the 10th time to reach the US Open last 16 as Canadian golden girl Eugenie Bouchard suffered a potentially tournament-ending head injury.
Five-time champion and world number two Federer claimed a 6-3, 6-4, 6-4 victory over his 29th-ranked German opponent.
The 34-year-old Swiss star, hoping to become the oldest champion since Ken Rosewall in 1970, will next face US 13th seed John Isner, who progressed after Czech opponent Jiri Vesely retired with a neck injury after dropping the first two sets.
Bouchard, meanwhile, was facing a battle to make her scheduled last-16 clash with Italy's Roberto Vinci on Sunday after injuring her head in a freak fall in the women's locker room on Friday.
The 21-year-old Canadian star withdrew from the women's and mixed doubles tournament on medical advice.
"The severity of the injury was and continues to be assessed by the on-site medical personnel at the US Open," said tournament director David Brewer.
"No determination about competing in the singles competition has been made at this time. Bouchard will continue with medical evaluation and treatment for the remainder of the day.
"An update on her condition will be provided later today."
Federer has now reached the fourth round in New York for the 15th year as he looks to return to the final for the first time since 2009.
His win was only marred by him dropping serve for the first time since Wimbledon.
"I won the big points today, I served well when I had to, even though it was up and down for both of us," said Federer, who will take a 4-1 career lead over Isner into their fourth-round clash.
"He stood far back to return so I had to do a reset in my mind."
Two-time runner-up Victoria Azarenka, the 20th seed, triumphed over 11th-seeded German Angelique Kerber in an Arthur Ashe Stadium thriller lasting almost three hours.
Azarenka, whose season has been blighted by a left thigh injury, won 7-5, 2-6, 6-4 on a sixth match point having trailed 2-5 in the first set.
The 26-year-old took her record over Kerber to 5-0 on the back of 51 winners to her opponent's 46 in a merciless contest of big-hitting.
Both players saved a combined 26 break points before the Belarusian prevailed to set-up a last-16 clash with America's Varvara Lepchenko.
"Angelique is a great fighter but I enjoy the hustle and getting winners and chasing down every ball," said two-time Australian Open champion Azarenka.
"I would stay here all day if I needed to win."
Later Saturday, Britain's Andy Murray, the champion in 2012, faces 30th seed Thomaz Bellucci of Brazil, who has reached the third round for the first time.
Fifth seed Stan Wawrinka, the French Open champion, is also looking for a last-16 place when he faces Belgian world number 107 Rubens Bemmelmans, who had never won a match in New York before this year.
Czech sixth seed Tomas Berdych, a semi-finalist in 2012, reached the last 16 for a fourth successive year by beating Spain's Guillermo García-Lopez 6-7 (2/7), 7-6 (9/7), 6-3, 6-3.
He next plays 12th seed Richard Gasquet, one of four Frenchmen in the last 16, who defeated Australia's Bernard Tomic 6-4, 6-3, 6-1.
Two-time Wimbledon winner Petra Kvitova, the Czech fifth seed, eased past Anna Karolína Schmiedlova of Slovakia 6-2, 6-1.
She next faces British qualifier Johanna Konta, the world number 97 who beat German 18th seed Andrea Petkovic 7-6 (7/2), 6-3.
Konta will be playing in her first Grand Slam fourth round.
Samantha Stosur, the 2011 champion and the last woman to beat Serena Williams at the tournament, battled past Italy's Sara Errani 7-5, 2-6, 6-1.
She next faces another Italian, 26th seed Flavia Pennetta, a 2013 semi-finalist, who put out world number 149 Petra Cetkovska 1-6, 6-1, 6-4.
Second-seeded Romanian Simona Halep later faces America's Shelby Rogers, a qualifier ranked at 154 in the world.