Somehow, 17 years after their first match and a 27th time facing each other in competition, Venus and Serena Williams have arguably never met with this much on the line — with history so squarely pinned atop the net between them.

And that’s saying a lot: These are sisters who have made history with every stroke of the racket in a sport once ruled by tradition. They have become ingrained in not only the American sporting lexicon, but that of our global cultural fabric, as well.

Tuesday, they’ll battle once more, as the U.S. Open’s top seed, world No. 1 and three-time defending champion Serena Williams takes on big sister Venus in the quarterfinals.

Will Venus be the one to stop Serena’s quest for the calendar Grand Slam — all four majors in one year?

“I don’t think anyone wants to be a spoiler,” Venus, 35, told reporters Sunday after her fourth-round win. “I think people love to see history being made. ... But at the same time, you’re focused on winning your match even though the circumstances are really much different than you.”

Not since Steffi Graf in 1988 has a tennis player — male or female — won the calendar Slam. American Maureen Connolly was the first woman to do it, back in 1953. Serena — amid her 21 career major titles –— has never put herself in that position.

Until now.

“I don’t really feel like if I win this tournament it’s going to make or break my career,” Serena, 33, said in her post-match news conference Sunday after defeating Madison Keys. “I look at it that way.”

Any way you look at it, it’s Serena who leads the head-to-head series with Venus 15-11, including six of the last seven matches.

But there is no player in the draw whom Serena respects — or perhaps fears — more.

“I’m playing, for me, the best player in the tournament, and that’s never easy,” Serena said. “She’s 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.”

It’s a match that is hardest for the Williams family to watch.

“It’s never easy,” said Isha Price, Venus’ and Serena’s sister. “I think they’re both happy to be in the place that they are. It’s toughest on my parents. It’s tough for us to watch, because you want the best for both of them.”

The best would be more history for Serena, who has a 52-2 record in 2015, including the Australian and French Open titles, another Wimbledon win, an uninterrupted stay at No. 1 and no fully realized rival. Belinda Bencic, a teenager who shocked Serena three weeks ago in Toronto, was ousted in the third round here — by Venus.

“They’re each other’s best friend. They love each other endlessly,” ESPN commentator Rennae Stubbs said. “They’re the same today with one another that they were 20 years ago. One of them is stopping the other from having a dream come true.”

Some underestimate the dream of Venus, who in 2011 was diagnosed with Sjogren’s syndrome, an immune deficiency, to still win Grand Slam tournaments. That’s what the seven-time major winner is after, even if her last Slam came in 2008. That year she beat Serena in the Wimbledon final, the last time in the sibling series that Venus won a Grand Slam match against her younger sister.

“They both want to win,” said Patrick Mouratoglou, Serena’s coach. “You can love the person on the other side of the net, but if you are a real competitor — which they both are — on a tennis court you forget and you play.”

Serena has been doing her best to forget all the talk this entire U.S. Open. The talk of the Grand Slam follows her everywhere she goes, and she has shrugged it off, time and time again.

Sunday, she did the same.

“I have to play Venus Williams next,” she said in a response to a question about going after the Slam. “I have to deal with that pressure first.”

Although neither would want to acknowledge it, this could well be the last time the sisters meet in the U.S. Open — or anywhere.

“We both know the draw, so we are both prepared to play each other,” Venus said. “It doesn’t always happen, but sometimes it does. Then we go. We go.”

Should Venus go one better, should she beat Serena in the U.S. Open during little sister’s quest for the Grand Slam, would a loss to her make it any easier for Serena to swallow?

Sort of.

“I would rather lose to Venus as opposed to anyone else,” Serena confirmed.

But then she added, “I, in general, don’t like to lose.”

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