Showing no mercy against her 82nd ranked opponent, Williams sent an ominous warning of her intention to add the US Open title to her recent wins at Wimbledon and the London Olympics with a rare 'double bagel' victory in 57 minutes.
"Andrea played really well today even though it was love and love," Williams said in a courtside interview. "I think I played really well today. I haven't played like that all tournament."
Williams won the last of her three US Open titles in 2008 but, on the evidence of her performances so far, a fourth title at Flushing Meadows appears well within her reach although her toughest challenges await.
The American's next opponent is Serbia's Ana Ivanovic, a former world number one who has rediscovered her best after a lean few years where she struggled with injuries.
Ivanovic advanced on Monday with an impressive 6-0 6-4 victory over Bulgarian Tsvetana Pironkova but said she would have to raise her game even higher to compete with Williams.
"She's obviously a great player and she's been playing the best out of all the girls on tour at the moment," said Ivanovic.
"Her serve is definitely her strength. I really have to be sharp from the first moment on and stay aggressive and stay in the moment."
Federer advanced to his 34th consecutive grand slam quarter-final without hitting a ball on the Labor Day holiday in the United States as Fish pulled with an undisclosed health issues.
"I am really sorry for Mardy," Federer said. "I just want to wish him a speedy recovery. We all want to see him back on tour soon."
The pair were due to clash in the fourth round but Fish, who missed part of the season because of a heart ailment and received treatment for an unspecified illness after his gruelling third round win over Gilles Simon on Saturday night, announced he was pulling out.
"I regret that I have to withdraw from the US Open for precautionary measures," the American said in a statement.
"I was reluctant to do so, but am following medical advisement. I had a good summer and look forward to resuming my tournament schedule in the fall."
World number one Federer has not dropped a set in this year's US Open at Flushing Meadows. The 31-year-old Swiss will now play Tomas Berdych after the Czech sixth seed thrashed Spain's Nicolas Almagro 7-6 6-4 6-1.
