Simon, a former world number six, has dropped to 66 in the rankings. But the 36-year-old Frenchman possesses guile to cause an upset.
However, Tsitsipas was too vigilant in their first meeting on the circuit and blew him off the court 6-1, 6-2, 6-1.
“I obviously wasn't expecting it to come so easy," said the Greek. "I was surprised.
Ease
"It was a great match from my side. I think I played a spectacular match from the beginning to the end."
Simon failed to fashion any break points on the Tsitsipas serve and hit only six winners compared to 26 from Tsitsipas who reached the semi-finals in Melbourne two years ago.
"I know I can press a lot with my forehand and also create damage on my backhand side, with my down-the-line backhand, which is my favourite shot,” added Tsitsipas.
“It has been giving me a lot of points and once it is there, I honestly feel very comfortable playing anyone.”
The 22-year-old will next take on the local hero Thanasi Kokkinakis, who breezed past Kwon Soon-woo of South Korea 6-4, 6-1, 6-1.
