On the eve of Tuesday's national day holiday, Hewitt was unable to fly the flag for Australia as he remained without a win in the one-way series since 2003.
Federer, seeking his fourth Melbourne Park title, will face off next against sixth seed Nikolay Davydenko, who triumphed after four hours over Spanish ninth seed Fernando Verdasco, 6-2, 7-5, 4-6, 6-7 (5-7), 6-3.
World number one Federer improved to 51-7 at the Open and 17-8 over Hewitt.
"I knew it would be extremely hard tonight, I was sweating bullets." said the Swiss, a winner in just under two hours. "I'm happy I'm through.
"He's a great competitor, he's playing really well again. I've had an incredible run against him, you won't get an easy match. I knew he would hang in there, he makes you get nervous. Tonight I was on the better side, so I'm happy."
Novak Djokovic moved closer to a potential second title at the event after his 2008 success, as he outclassed Pole Lukasz Kubot 6-1, 6-2, 7-5.
Djokovic wasted little energy with 11 aces, 37 winners and six breaks of serve over his 86th-ranked opponent, who advanced in a walkover in the third round at the weekend.
"I'm happy with the way things are going," said the Serb. "The surface is quite suitable to my game."
"I won this tournament two years ago, so I just look forward to the upcoming challenges. I'm ready to give my 100 percent and try to get a step further."
Davydenko has not been beaten since November 23, 2009, in his first group match at the year-end championships in London, an event which he went on to win by beating both Federer and Rafael Nadal.
The Russian sixth seed has polished his workmanlike reputation with unexpected blasts of personality during his run in Melbourne, suddenly blossoming into a minor personality.
"I'm really tired. It was difficult play him," said Davydenko, who broke 4-2 for victory in the final set. "I believe I'm still strong mentally. I don't know if I can win (the title) here, but my tennis is working well."
Frenchman Jo-Wilfried Tsonga, losing finalist to Djokovic two years ago, won a marathon against Spain's Nicolas Almagro 6-3, 6-4, 4-6, 6-7 (6-8), 9-7 on the back of 25 aces and 77 winners.
In the women's fourth round, holder Serena Williams led the American seeded sister act, running down Aussie 13th seed Samantha Stosur 6-4, 6-2.
"It's important when you're playing a local girl to not let the crowd get too involved or else they'll kill you," said defending champion Williams. "I knew going into the match I had to serve well against Sam.
"Today was my best match so far in this tournament. I just hope I can keep it up," said the American after avenging a loss to Stosur from last summer.
Venus Williams booking her last-eight spot with a comeback over Italy's Francesca Schiavone 3-6, 6-2, 6-1 And next faces China's Li Na, who swamped Danish fourth seed Caroline Wozniacki 6-4, 6-3.
Li holds a 1-0 record over sixth-seeded Williams, defeating her in the Beijing quarter-finals two years ago.
Williams overcame a poor start against Schiavone, turning the tables to survive as the major began its concluding second week.
"She played really well in the first set, I have to give her credit," said Williams, a five-time Wimbledon winner. "She just played really aggressively, doing everything she needed to do to win the match."