Williams remained on course for a seventh Australian Open crown and 23rd career Grand Slam title with a 7-5 6-4 victory over Czech 16th seed Barbora Strycova.
The 35-year-old American will play British No 1, Johanna Konta, in the quarter-final.
Konta, who is seeded ninth at Melbourne Park, had little trouble in racing through the opening set before showing tremendous composure in the second.
Trailing 4-1, the 25-year-old reeled off five games in succession to wrap up a fourth consecutive straight sets victory and book a place in the last eight of the Aussie Open for a second successive year.
For Williams, whose older sister, Venus, in the last eight on opposite sides of the draw, a first all-Williams major final since 2009 at Wimbledon remains a possibility.