Roger Federer will begin his bid to equal Pete Sampras's record of 14 Grand Slam titles against Italian Andreas Seppi in the first round of the Australian Open next week.
Top seed Rafael Nadal, who snapped Federer's record 237-week stint as world number one last August, will meet Belgium's Christophe Rochus after the draw was made at Melbourne Park on Friday.
Champion Novak Djokovic was drawn to meet a qualifier in his opening match but if the seeds live up to their billing, he could be on another collision course with Federer in the semi-finals.
Fourth seed Andy Murray, tipped to end Britain's 73-year wait for a men's Grand Slam champion, was slotted into the same half of the draw as Nadal and will open his account against Romania's Andrei Pavel.
Federer will need to be on his guard if he is to win a fourth trophy in Melbourne since his path is littered with banana skins, including a potential second round match with former world number one Carlos Moya.
If he survives that test, Marat Safin could be his next opponent. The Russian beat the Swiss en route to the 2005 title.
Seventh seed Andy Roddick and Argentina's David Nalbandian, the 10th seed, could face off in an intriguing fourth round battle.
Lleyton Hewitt's chances of adding to his two Grand Slam crowns looked slim after he was drawn to face 2007 runner-up Fernando Gonzalez of Chile in the first round.
The match was greeted with an audible sigh by the assembled local media and tournament volunteers, though tournament director Craig Tiley said fan interest would still be high should Hewitt be knocked out early.
"It's a tough draw, but Lleyton is playing good tennis and he can cope with the conditions," Tiley told reporters.
"The quality of matches in the first round and throughout the tournament are still really high."
Tiley said ticket sales were "tracking to the same level as last year."
Women's world number one Jelena Jankovic, entering a Grand Slam for the first time as the top seed, will open her campaign against Austria's Yvonne Meusburger.
Serena Williams, who defeated Serbia's Jankovic in the 2008 US Open final and is the second seed at Melbourne Park, will play Yuan Meng of China.
The American, targeting a fourth title in the season's opening major, faces a tricky passage through the draw as she could run into 2006 champion Amelie Mauresmo in the fourth round before setting up a possible semi-final with sister Venus.
Russian pair Dinara Safina, seeded third, and fourth-seed Elena Dementieva, the Beijing Olympic champion, will play Alla Kudryavtseva and Kristina Barrios respectively.
Safina was drawn in the top half with Jankovic.
Last year's champion Maria Sharapova withdrew from the tournament with a shoulder injury, while runner-up Ana Ivanovic was picked to face Julia Goerges of Germany.