The Williams' sisters have not met this early in a Grand Slam since 1998.
Serena Williams 6-2, 6-2 win on Wednesday night means she will advance to the third round of the U.S. Open where she will face Venus. The Williams' sisters third-round meeting is earlier than they have met in a Grand Slam in 20 years.
Venus, the 16-seed, beat Camila Giorgi 6-4, 7-5 earlier in the day on Wednesday. Serena defeated an un-seeded Carina Witthoft, 23, of Germany on Wednesday evening.
Serena, a six-time U.S. Open champion, was given a seeding boost by officials after her maternity leave. Williams, ranked 26th, was boosted to the tournament's No. 17 seed, one spot below older sister Venus, a two-time U.S. Open winner.
The last time the two have played this early in a Grand Slam tournament was in 1998 at the Australian Open in their first-ever meeting on the tour.