Seven of Williams' nine victories over Hantuchova have come at Grand Slam events -- Hantuchova's only win was here in the third round in 2006.
Rod Laver Arena was about three-quarters full for the match, though it was a quiet crowd -- people seemed to be expending more energy fanning themselves with programs and newspapers than applauding points on the court.
There were a few shouts of encouragement when Williams broke early in the second set, but the crowd grew more vocal when Hantuchova broke back in the sixth game to make it 3-all.
No. 9 Angelique Kerber advanced earlier with a 6-3, 6-4 win over American Alison Riske, and said her main aim had been to "get off the court before it became really hot." Kerber will next play No. 28 Flavia Pennetta, who advanced 6-1, 7-5 over Mona Barthel of Germany.
In an early men's result, Florian Mayer beat No. 20 Jerzy Janowicz 7-5, 6-2, 6-2.
Matches on outer courts were suspended for four hours on Thursday afternoon when the Extreme Heat Policy was invoked for the first time in the tournament. Lightning and rain caused further delays later in the evening. Maria Sharapova advanced after playing 3 ½ hours in the blazing sun, before the roof was closed on Rod Laver Arena.
Two-time defending champion Victoria Azarenka won her night match indoors. The loaded top half of the men's draw lost a contender when No. 5 Juan Martin del Petro lost a second-round match that ended at 1:20 a.m. Friday. Rafael Nadal, Andy Murray and Roger Federer all progressed earlier on day four.