Serena and Venus Williams pulled double-duty on Friday, winning two matches apiece at the rain-disrupted WTA claycourt event in Charleston to book a semi-final showdown.
The Williams sisters will face each other across the net for the first time since 2009.
Both played twice on Friday, after a lengthy rain delay on Thursday saw four third-round matches postponed.
Top seed and defending champion Serena defeated American Mallory Burdette 6-4, 6-2 in the third round, then returned to beat sixth-seeded Czech Lucie Safarova 6-4, 6-1 in a rematch of last year's final here.
Serena rallied from a 2-4 deficit in the opening set, winning the last four games to finish off the frame and giving Safarova little opportunity in the second.
Venus Williams, seeded fifth, beat American Varvara Lepchenko 6-2, 4-6, 6-2 to reach the quarter-finals, and followed up with a 6-4, 6-4 victory over Madison Keys.
Although the scoreline against Keys looked more routine, Williams had to rally from an early break down in each set.
Serena Williams said she was motivated by seeing her older sister come through both of her matches.
"I figured if she can win two matches, I have no excuse not to win my two matches," Serena said. "It's actually not that bad to play two matches in one day -- it's not ideal, but I play doubles all the time, and so I looked at it like, 'OK, I play singles and I play with Venus in doubles the same day.' So really that's how I looked at it."
The Williams sisters haven't played each other since Serena triumphed over Venus in the final of the WTA Tour Championships at Doha in 2009. Serena beat her older sister in the Wimbledon final earlier that year.
They last met on clay in the 2002 French Open final won by Serena, who leads their career head-to-head 13-10.
"It definitely feels like a long time ago," Serena said. "But Venus is the toughest opponent I've ever played.
"I think she's beaten me the most out of any player. I know her game and she knows my game. I think it'll be a great match tomorrow."
Ninth-seeded Serbian Jelena Jankovic also secured a semi-final berth, with a 6-2, 6-1 victory over Canadian Eugenie Bouchard.
Jankovic's victory was her 500th career match win, a statistic she wasn't aware of until after the contest.
"I had no idea how many wins I had," she said. "But it's pretty nice. It's a great achievement to get my 500th win, and hopefully I can have many more."
Jankovic next faces Switzerland's Stefanie Voegele, who beat second-seeded Dane Caroline Wozniacki 3-6, 6-4, 6-3.
Wozniacki was up a break at 3-2 in the third set but lost the last four games.