Mark Philippoussis fired a warning to the rest of the field as he beat 2002 winner Thomas Johansson.
The Australian 10th seed was in excellent form as he won 7-6 6-2 7-6, delivering booming serves and powerful ground strokes in a high-quality match.
Johansson, who was making his return from surgery, battled well in the first set, but succumbed to an unstoppable Philippoussis in the second.
In a closer third set, Philippoussis raised his game at just the right time.
Philippoussis' compatriot, and 15th seed, Lleyton Hewitt reached round two as his opponent retired hurt for the third straight match.
Hewitt was leading Cecil Mamiit 6-2 6-4 when the American collided with the umpire's chair and injured his foot.
Mamiit tried to continue after receiving attention, but was forced to continue one game later.
Carlos Moya hurt his ankle in the final of last week's Adidas International against Hewitt, while Martin Verkerk pulled out of the semi because of dizziness.
Third seed Juan Carlos Ferrero had one of the easiest routes through as he lost just two games in his match against Albert Montanes.
Ferrero won the match 6-0 6-1 6-1.
Another of the favourite for the tournament, David Nalbandian, also had an easy win, beating Brazilian debutant Ricardo Mello 6-2
Nalbandian beat Andre Agassi in the final of last week's Kooyong Classic and is clearly in good touch.
But Spain's Felix Mantilla joined the exodus of seeds falling in the first round as he lost to Frenchman Thierry Ascione.
The 23rd seed lost 7-5 6-1 7-6 (7/3) to Ascione, who is ranked 87th in the world and was playing at Melbourne Park for the first time in his career.
It was the sixth time in eight visits to the Australian Open that Mantilla has lost in the first round.
Ascione will now play Rafael Nadal, who beat Michal Tabara, in the next round.
The 25th seed, Jonas Bjorkman, is also out of the tournament.
Bjorkman, who beat Tim Henman on his way to the last eight in Melbourne two years ago, lost out to Armenia's Sargis Sargsian 6-2 6-3 6-1.
Another seed out in the first round is Feliciano Lopez, who was beaten by Alberto Martin.
The Spaniard came back from two sets down to beat the 28th seed 3-6 4-6 7-6 (7/3) 6-4 6-2.
But 14th seed Jiri Novak had no such trouble, easing to a 6-3 6-3 7-5 win over Olivier Rochus.