Serena Williams beat Germany's Carina Witthoft 6-3, 7-6 in the round of 64 on Wednesday at the USTA Billie Jean King National Tennis Center in New York. Venus Williams edged Italy's Camila Giorgi 6-4, 7-5 to advance to the sister duel.
"I wouldn't say it's exciting, but it's definitely going to be a really tough match for me," Serena Williams told reporters. "It's early in the tournament but it is what it is."
"Unfortunately -- and fortunately -- we have to play each other. We make each other better. We bring out the best when we play each other. It's what we do. I think we are used to it now."
The last time the Williams sisters faced off in a Grand Slam, Serena beat Venus in straight sets in the 2017 Australian Open final. Serena was two months pregnant at the time.
Serena holds a 17-12 head-to-head record against Venus. She beat Venus in three sets in the quarterfinals at the 2015 U.S. Open. Venus hasn't beaten Serena in a Grand Slam since the 2015 Wimbledon final.
No. 3 Sloane Stephens beat Anhelina Kalinina in three sets on Wednesday. No. 7 Elina Svitolina beat German Tatjana Maria and No. 9 Julia Goerges beat Russian Ekaterina Makarova. No. 8 Karolina Pliskova also won her second-round match against Romanian Ana Bogdan to advance.
On the men's side, Andy Murray fell to No. 31 Fernando Verdasco in four sets. No. 1 Rafael Nadal topped Canadian Vasek Pospisil. No. 3 Juan Martin del Porto beat American Denis Kudla in three sets. No. 9 Kevin Anderson beat Jeremy Chardy. No. 9 Dominic Thiem also eliminated American Steven Johnson.