Kyrgios will play Radu Albot in his opener while Alex de Minaur will look to get past Taro Daniel, a resurgent Jason Kubler has a big task ahead in 19th seed Roberto Bautista Agut, James Duckworth faces Andy Murray, Jordan Thompson meets Cameron Norrie, John Millman has Jenson Brooksby to get past in his opener.
The Aussie women openers see Ashleigh Barty, seeded 18, facing a qualifier in the opening round but with a potential match with 12th seed Garbine Muguruza in the third round.
Daria Gavrilova plays Spaniard Sara Sorribes Tormo while Samantha Stosur has the toughest of opening matches against second seed Caroline Wozniacki. Lizette Cabrera will meet Ajla Tomljanovic in an all-Aussie matchup.
Serena and Venus Williams could be headed toward their earliest grand slam meeting in 20 years, facing a potential third-round match-up at the US Open. If the sisters do play each other, the winner might face world No.1 Simona Halep in the fourth round.
Serena's opener comes against 60th-ranked Magda Linette while Venus faces a tricky first-round match against wildcard Svetlana Kuznetsova, whose two major championships include the 2004 US Open.
In the men's field, No.1-ranked and defending champion Rafael Nadal opens against compatriot David Ferrer in a rematch of their 2013 French Open final. No.2 Roger Federer plays Yoshihito Nishioka in the first round.
Federer faces a potential quarter-final against No.6 seed Novak Djokovic, the Wimbledon champion who beat him two weeks ago in a tune-up and is considered the tournament favourite.
Fourth seed Alexander Zverev and seventh-seeded Marin Cilic, the 2014 US Open champion, are also in Federer's half of the draw along with Kyrgios.
Stan Wawrinka, the 2016 US Open champion who missed last year's tournament because of injury and was given a wildcard into this year's field, faces No.8 seed Grigor Dimitrov in one of the headline matches of the first round. Wawrinka, a three-time major titlist, eliminated Dimitrov in the first round at Wimbledon in June.
Nadal's half of the draw includes No.3 seed and 2009 US Open champion Juan Martin del Potro - who could face another former champion in Andy Murray in the third round - and fifth-seeded Kevin Anderson, the Wimbledon and US Open runner-up.
Besides Federer-Djokovic, the other possible men's quarter-finals are Nadal-Anderson, Del Potro-Dimitrov and Zverev-Cilic.
