Unlike her earlier sluggish matches, Serena was in the zone from the off against the dangerous Slovak, a steely look in her eyes as she walked onto Rod Laver Arena soon after Venus lost to Keys.
The powerful world number one blasted 15 aces to pummel the 11th seed 6-2 6-2 in just over an hour and make her 26th Grand Slam semi-final. She has gone on to win 18 major titles.
Long-time rival Maria Sharapova made the last four yesterday and will face fellow Russian Ekaterina Makarova.
The unseeded Keys, 19, is the tournament surprise package, battling hard to beat a resurgent Venus 6-3 4-6 6-4 and end any chance of the sisters meeting in a Grand Slam semi for the first time since Wimbledon 2000.
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Keys did the job despite carrying a left thigh injury, needing a medical timeout in the second set for treatment.
Among the men, Andy Murray and Tomas Berdych are already safely into a semi-final showdown after beating Nick Kyrgios and Rafael Nadal respectively yesterday.