Caroline Wozniacki, derailed this year by an ankle injury which sent her career into a tailspin, and Anastasija Sevastova, who quit the sport three years ago, set up a US Open quarter-final duel Sunday.
Former world number one Wozniacki, the runner-up in 2009 and 2014, downed American eighth seed Madison Keys 6-3, 6-4 to make the last-eight in New York for a fifth time.
Sevastova became the first Latvian woman in 22 years to reach a Grand Slam quarter-final when she beat British 13th seed Johanna Konta 6-4, 7-5.
The other quarter-final in the bottom half of the draw sees German second seed Angelique Kerber face Roberta Vinci, the Italian seventh seed.
Kerber defeated Petra Kvitova 6-3, 7-5 while Vinci enjoyed a 7-6 (5), 6-2 win over Lesia Tsurenko of Ukraine.
Now ranked at 74 in the world after a right ankle injury sidelined her for almost three months, Wozniacki hit just seven unforced errors in her win over Keys.
Wozniacki is back in the last-eight of a Slam for the first time since making the semi-finals in New York in 2014.
“After such a tough year, it’s amazing to be in the quarter-finals,” said the 26-year-old, whose Grand Slam record this year had seen first-round losses in Australia and Wimbledon while she sat out Roland Garros.
Sevastova, the 26-year-old world number 48, knocked out French Open champion and third seed Garbine Muguruza in the second round and she built on that victory on Arthur Ashe Stadium in a last 16 tie which featured 12 breaks of serve.
Larisa Savchenko was the last Latvian woman to make the quarter-finals of a Slam at Wimbledon in 1994.
Sevastova had not won a match in New York since 2010 before this year and with her career unravelling, she quit in May 2013 to study leisure management in Austria.
She returned to the sport in January 2015 and that decision has been fully vindicated by her stunning run.
“I had a lot of injuries. I was depressed and it just wasn’t fun anymore, but now I’m back,” said Sevastova when asked why she turned her back on the sport.
Konta, bidding to become the first British woman in the quarter-finals since Jo Durie in 1983, never recovered from a poor start.
A semi-finalist at the Australian Open in January, the 25-year-old was 3-0 down in the first set and 4-1 behind in the second.
She managed to save a match point in the ninth game of the second set but Sevastova held her nerve to secure victory after 1 hour and 42 minutes,
Wozniacki defeated Sevastova in their only previous meeting, in straight sets in the Australian Open last 16 in 2011.
Australian Open champion Kerber defeated two-time Wimbledon champion Kvitova as she looks to improve on her best showing in New York of a semi-final spot in 2011.
Kvitova served up a seventh double fault of the tie to hand Kerber victory having committed 43 unforced errors.
Vinci, the 2015 runner-up, reached the quarter-finals for the fourth time but had to shrug off a tendon injury in her leg to prevail.
“I love to play here. The atmosphere, the crowd, everything is great,” said Vinci who knocked out Serena Williams in the semi-finals in 2015 before losing the final to compatriot Flavia Pennetta.
Kerber and Vinci are 2-2 in head-to-head meetings but haven’t played since Beijing in 2013.
The remaining four last-16 matches take place on Monday when world number one and six-time winner Serena Williams tackles Yaroslava Shvedova of Kazakhstan.
Carla Suarez Navarro meets Simona Halep while Agnieszka Radwanska takes on teenager Ana Konjuh and two-time champion Venus Williams faces Karolina Pliskova.