Flushing Meadows is expected to be buzzing on Tuesday night when the most famous tennis sisters of all-time meet in the quarterfinals, as top-ranked Serena Williams takes on sister Venus at Arthur Ashe Stadium. The pressure will be on the younger sister, Serena, who is attempting to win a calendar Grand Slam after winning the Australian Open, French Open and Wimbledon this year and entered the U.S. Open as a 4/5 favorite to win the title.

Venus, ranked No. 23 at age 35, overcame some difficult tests in the opening rounds, edging Monica Puig and Irina Falconi, but earned straight-sets wins over No. 12 seed Belinda Bencic in the third round and Anett Kontaveit in the fourth round. Venus defeated Serena the last time the two met on hardcourt in a three-set semifinal at the 2014 Rogers Cup in Montreal.  

But Serena, 33, owns a stellar 52-2 record in 2015, and has been in top form in New York. She dropped a set to Bethanie Mattek-Sands in the third round, but cruised to a straight-sets win over No. 19 Madison Keys in the fourth round, 6-3 6-3.

Venus has already stated that she is playing the role of "spoiler" when she takes on her younger sister. Venus would later add that she thinks "people love to see history being made."

"She's a player who knows how to win, knows how to beat me, and knows my weaknesses better than anyone," Serena said of her older sister.

Serena owns a 15-11 head-to-head record over Venus. Serena is favored in the match at -1000 compared to +650 for Venus.

Start Time: 7 p.m. ET

TV Channel: ESPN

Live Stream: WatchESPN

Prediction: Serena in three sets