It was total domination for second-seeded Williams, who looked at ease in winning back-to-back Grand Slam titles and was moving fluidly on the court.
It was a sharp contrast to No. 3 Safina, who was tight from the start.
In the first game, Safina double-faulted three times, including on break point. Williams ran off 18 of the last 20 points in the first set to finish it in 22 minutes.
Other than matches that ended early due to illness or injury, it was the most lopsided Australian Open women's final since 1962, when Margaret Smith beat Jan Lehane 6-0, 6-2.
It was Williams' second overwhelming victory in a final at Melbourne Park, where she kept alive her record of winning in odd-numbered years since 2003. Coming into the 2007 tournament unseeded after being plagued by injuries the year before, she beat top-seeded Maria Sharapova 6-1, 6-2.
Sharapova rebounded to win last year but was unable to defend her title while recuperating from a shoulder injury.
After Melbourne's hottest three-day heat wave on record, conditions were nearly perfect for the tournament's first women's final at night, but Rod Laver Arena was less than capacity, with large patches of empty seats scattered around the upper deck of the 15,000-seat stadium.
On Sunday, top-ranked Rafael Nadal will face No. 2 Roger Federer in the men's final. Federer will be trying to tie Pete Sampras' record of 14 major titles, while Nadal is seeking his third Grand Slam out of the last four, missing only the U.S. Open last September that was won by the Swiss star.