In cool and cloudy conditions, the Swiss was irresistible on Rod Laver Arena as he banished 97th-ranked Slovakian Lukas Lacko 6-1, 6-1, 6-3 with trademark grace and aggression.
The world number two broke Lacko's serve seven times and hit a stream of 37 winners and just 18 unforced errors to polish off the Slovak in just 1hr 24min.
A fifth Open win for Federer, 29, would also stop top-ranked Rafael Nadal, his long-time nemesis, completing the first sweep of all four major titles in more than 40 years.
"I was able to keep on pressing and put him on the back foot. For me it was no surprise he started to get into the match at one stage in the third set," Federer said.
"I thought it was a good match. I don't think he played too bad himself. I saw some talent in him, too, and that's why I was really happy I chose that tactic early on to pressure him. That it worked was obviously great."
Federer will face either Gilles Simon of France or Taiwan's Lu Yen-Hsun in the next round as he bids to become only the second man, after Australia's Roy Emerson, with five or more Open wins.
Top-ranked Nadal, whose "Rafa Slam" would unite the major trophies for the first time since Australia's Rod Laver won all four in 1969, plays Marcos Daniel of Brazil in his opening match.
Meanwhile, America's number one Andy Roddick went through in straight sets and Gael Monfils of France came from two sets down to oust injured Dutchman Thiemo De Bakker.
But it was a disastrous day for Russia's Nikolay Davydenko, the 23rd seed and a quarter-finalist last year, who crashed out against Germany's Florian Mayer 6-3, 4-6, 7-6 (7/4) 6-4.
"I tried to fight because my tennis was not so great," said Davydenko, 29.
"But it was not enough, I am not young any more."
America's Sam Querrey, the 18th seed, was also sent packing in a five-set upset defeat to Poland's Lukasz Kubot.
Czech sixth seed Tomas Berdych went through in straight sets and American Mardy Fish recovered from two sets down to beat Victor Hanescu.
In the women's draw, wide open after five-time champion Serena Williams pulled out injured, her sister Venus Williams overcame a slow start to overpower Italy's Sara Errani 6-3, 6-2.
Williams, who used an inhaler between games, was untroubled by the fact she has not played a tour event since the US Open in September, and warmed up only with an exhibition tournament in Hong Kong.
"It's only just a matter of believing that I can come out and play well even though I haven't played as much as my opponents," she said. "I worked as hard as I could in the off-season -- I worked hard to be here."
Top seed Caroline Wozniacki was unconvincing in a 6-3, 6-4 win over Argentina's Gisela Dulko, while French Open champion Francesca Schiavone and 2008 winner Maria Sharapova also had some uncomfortable moments.
Wozniacki, under pressure to claim a maiden Slam title to show critics she is a deserving women's number one, took 1hr 40min to claim her first victory since being shocked in her first match at the Sydney International.
Sharapova, pursuing a lengthy comeback from injury, admitted she was jittery during her 6-1, 6-3 win over Thailand's Tamarine Tanasugarn after last year's shock first-round exit.
"I was definitely a little bit nervous in the beginning," said the former women's number one. "Last year I played the first match on centre court and I lost, so I was like, I don't want this to happen again this year."
Schiavone, the sixth seed, came from a set down to beat Arantxa Parra Santonja of Spain 6-7 (4/7), 6-2, 6-4.
Belgium's Kim Clijsters is considered favourite to add the Australian title to her US Open crown, but faces a tough first-round assignment against Russia's Dinara Safina, the 2009 finalist here.