Serena Williams, chasing a calendar Grand Slam, seeks a US Open quarter-final spot that could be against her sister Venus while top-rated Novak Djokovic also tries to advance on Sunday.
Top-ranked Serena Williams needs only four more triumphs to complete the first calendar Slam since Steffi Graf in 1988.
Williams, holder of all four major titles, also seeks her 22nd career Slam singles crown to match Graf's Open Era record.
But tension has mounted at Arthur Ashe Stadium as Williams has struggled through her past two matches, battling to keep her focus early before finding her top form with her formidable serve.
"I'm not trying to live on the edge," said Williams, who is 10-0 in three-setters at Grand Slams this year.
Serena Williams, 33, will face US 19th seed Madison Keys while sister Venus, 35, takes on 152nd-rated Estonian qualifier Anett Kontaveit.
If the siblings both win, it will set up their 27th career meeting on Tuesday and their fifth at the US Open, with Serena holding a 15-11 all-time edge after winning their most recent match in July at the fourth round of Wimbledon.