"It feels good for the match to be over with," Serena told reporters. "Win or lose, it just feels that that's done."
"I think it's the best match she has ever played against me," Venus said. "I don't think I did a lot wrong, but she just did everything right. Obviously at that level is definitely where she is going to want to stay during this whole tournament."
No. 7 Elina Svitolina also beat Wang Qiang in straight sets. No. 3 Sloane Stephens beat Victoria Azarenka 6-3, 6-4 and No. 8 Karolina Pliskova eliminated Sofia Kenin.
On the men's side, No. 1 Rafael Nadal outlasted No. 27 Karen Khachanov. No. 5 Kevin Anderson also won his marathon match against No. 28 Denis Shapovalov. No. 9 Dominic Thiem beat Taylor Fritz. No. 11 John Isner beat Dusan Lajovic.
Kanepi seeks to beat Williams after upsetting world No. 1 Simona Halep in the first round. She has yet to drop a set at the Grand Slam.