Serena fired six aces and won 80 percent of her first serve points to advance to the quarter-finals in emphatic style.
She could eventually face a semi-final showdown with elder sister Venus, who rallied from 2-4 down in her opening set to beat Australian Anastasia Rodionova 7-5, 6-2.
"I hope we both get there," said Serena, who must get past big-hitting German Sabine Lisicki, the sixth seed, in the quarter-finals.
"I have to win another match, and I really, really hope we both get there, so we'll see."
Lisicki rallied from a break down in both sets to beat Kazakhstan's Yaroslava Shvedova 7-5, 6-4.
This is the third time both Williams sisters have played the WTA tournament in Charleston in the same year, but the first time both have made the quarters in the same year.
Venus will have to wait until Friday to find out who she faces in the quarter-finals after heavy storms moved into the area and halted play for the night as second-seeded Samantha Stosur led unseeded Galina Voskoboeva of Kazakhstan 4-2.
Stosur, the US Open champion ranked fifth in the world, was left as the highest-ranking player in the field after the injury withdrawal on Sunday of Agnieska Radwanska, just a day after her triumph in Miami.
Marion Bartoli, the third seed from France, was toppled 6-4, 1-6, 6-4 by 14th-seeded Polona Hercog of Slovenia.
Hercog set up a quarter-final clash with Russian Nadia Petrova, a 6-1, 6-4 winner over eighth-seeded Anastasia Pavlyuchenkova of Russia.
Fourth-seeded Russian Vera Zvonareva and Czech ninth seed Lucie Safarova set up a quarter-final match-up.
Zvonareva beat Switzerland's Stefanie Voegele 5-7, 6-3, 6-4 and Safarova defeated Canadian Aleksandra Wozniak 6-2, 6-7 (4/7), 6-1.
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