The defending champion, who is seeded No. 2, moved on with a one-sided 6-2, 6-0 win over 22nd-seeded Daniela Hantuchova of Slovakia.
Williams hit 27 winners and eight aces in the fast-moving match.
The American star, who won the year's first major, the Australian Open, and the third, Wimbledon, is shooting for her third U.S. Open title and 12th Grand Slam win overall.
Copyright 2009 by United Press International.
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