PHOTO: REUTERS
In the 27th episode of a family rivalry which had its first public airing at the 1998 Australian Open, world number one Serena tackles 23rd-ranked Venus boasting the upper hand.
Serena, two years younger than Venus at 33, leads the head-to-head record at 15-11 with an 8-5 edge in Grand Slam meetings.
They have split four US Open meetings, including Venus winning the 2001 final and Serena taking a 2002 rematch.
But this time around, the stakes are higher as Serena is just three wins shy of completing the first calendar Grand Slam of all four majors since Steffi Graf in 1988.
If she wins Saturday, it will be her 22nd Slam singles title, matching Graf's Open Era record and just two shy of Margaret Court's all-time mark.
"The only player in the draw I don't want to play, not only because she's my sister, but for me she's the best player," Serena said of Venus.
"She has beaten me so many times. She's a player that knows how to win, knows how to beat me and knows my weaknesses better than anyone."
The two met as recently as July at Wimbledon, where Serena claimed one of many routine wins in the rivalry, which often fails to live up to the hype.
Venus wants to add to a trophy collection that includes the 2000 and 2001 US Opens and five Wimbledon titles, the most recent in 2008.
"I would love to. But it's easier said than done," Venus said.
"Even though you're playing your sister you have to be prepared and focus. The preparation doesn't change."
Serena's current 32-match Grand Slam win streak includes a Wimbledon title run to complete a "Serena Slam" and make her the oldest major champion at age 33.
The build-up to Tuesday's encounter has been no different with player after player -- man or woman -- probed to exhaustion on their thoughts on the match-up.
"I admire what they're doing for so many years to play against each other on such a big stage," said men's world number one Novak Djokovic, who follows the sisters onto Arthur Ashe Stadium on Tuesday night for his quarter-final against Feliciano Lopez.
"It's strange. They grew up together playing tennis. Of course they love each other, but then very have to be professional and go out on the court and play each other so many times in the finals of Grand Slams.
"They both were No. 1s of the world.. but I don't know if I'll be able to play my brother. It's not possible. I would not be able to handle on the court."
Adding to the intrigue of Tuesday's occasion is the fact that it's exactly 14 years to the day after the sisters met in their first Grand Slam final at Arthur Ashe Stadium.
Not surprisngly, Williams v Williams XXVII has overshadowed the day's other women's quarter-final between unseeded duo, Kristina Mladenovic and Roberta Vinci.
The Frenchwoman and her Italian rival have taken full advantage of exploiting the quarter of the draw from which Maria Sharapova excused herself through injury on the eve of the tournament.
Djokovic, meanwhile, will be playing his 26th consecutive Grand Slam quarter-final as he continues his push towards a 10th major and third of the year after the Australian Open and Wimbledon.
Tuesday will represent his ninth successive US Open quarter-final slot while 33-year-old Lopez is playing in his first at the 14th attempt.
Lopez, the 18th seed, said Djokovic will hold the cards, having won all of the pair's five meetings.
The left-hander has only ever taken one set off Djokovic and that was in their first meeting at the 2007 Australian Open.
Lopez knocked out Fabio Fognini, the conqueror of 14-time major winner Rafael Nadal in the last round.
Nadal's shock exit was followed by an even more seismic event on Monday when third seed Andy Murray was dumped out by Kevin Anderson in what was the 2012 champion's earliest Slam exit in five years.
Tuesday's other men's quarter-final will see defending champion Marin Cilic, the ninth-seeded Croatian, face France's 19th seed Jo-Wilfried Tsonga.
Cilic has a 4-1 career lead over Tsonga in main tour matches, winning the pair's last three without dropping a set.
Serena v Venus - five facts
Five facts on Tuesday's US Open quarter-final between Serena and Venus:
- Serena and Venus have met 26 times, with Serena holding a 15-11 advantage overall, including 8-5 at Grand Slams. At the US Open, their series is tied 2-2
- The sisters are meeting at a Grand Slam for the 14th time. Only Chris Evert-Martina Navratilova met more often at the Slams (22)
- While Serena won their last meeting, on grass at Wimbledon, Venus won their last hardcourt meeting -- just over a year ago, in the Montreal semi-finals
- In semi-finals and finals, Serena leads 12-6, but Venus actually leads 5-3 in all other matches
- The most one-sided scoreline was Serena's 6-1, 6-2 win in the semi-finals at Charleston in 2013. The only 6-0 set in the series occurred in round-robin action at the 2008 WTA Finals, with Venus a 5-7, 6-1, 6-0 victor.
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