The imposing world number one and top seed stormed through her match in oven-like conditions on Rod Laver Arena, crushing Serbia's Vesna Dolonc 6-1, 6-2 in just 63 minutes.
Williams is the firm favourite ahead of defending champion Victoria Azarenka to win a sixth Melbourne crown, and the American reinforced her credentials with a customary towering performance.
Now 32, she denied being favourite added any pressure, having been in similar positions many times before.
"But for me, I look at it as kind of exciting that I have an opportunity to go all the way.
"But with that being said, I have so many matches I have to win in order to do well and in order to lift the trophy. It's such a long way."
The victory was yet another landmark for the American veteran, who is gunning to match the achievement of Chris Evert and Martina Navratilova in winning her 18th Grand Slam title.
Williams has now played 68 times at Melbourne Park, with only Lindsay Davenport on 69 having graced the Australian courts more in the Open era.
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