Next Gen Finals champion Tsitsipas enjoyed a breakthrough 2018 campaign and has surged to a career high ranking of 15.
Federer, making his 20th Melbourne appearance, is expecting a clash of styles against Tsitsipas, who pushed the Swiss maestro to two tiebreaks at the Hopman Cup earlier this month.
“I’m happy I played against him at the Hopman Cup. I think he played really well there. I actually did too. I thought it was really high-quality tennis,” the 37-year-old told reporters.
“This is obviously a different type of match, it being best of five, it being a fourth round of a slam, where we know now how we feel on this court.
“I like how he mixes up his game and also comes to the net – so will I. I think we will see some athletic attacking tennis being played.”
Big-hitting Czech Tomas Berdych, who spent a big chunk of last season on the sidelines with a back injury, will look to renew his rivalry with second seed Rafa Nadal.
Nadal has a 19-4 head-to-head advantage, but Berdych will hope for a repeat of his Melbourne quarter-final win in 2015.
Ashleigh Barty, bidding to become the first home winner of the Australian Open since Chris O’Neill in 1978, will face her biggest test when she takes on a rejuvenated Maria Sharapova.
The Russian displayed her title credentials with a commanding third-round performance to knock out last year’s winner Caroline Wozniacki.