Sinner raced to a 6-1, 6-3, 7-6(2) victory and faces United States eighth seed Ben Shelton or Norway's 12th-seeded Casper Ruud for a place in the semi-finals.
The world number two is bidding to win the Melbourne crown for a third time in a row, something only Novak Djokovic has done in the Open era (since 1968).
Djokovic and Sinner are on course for a blockbuster last-four showdown.
"It was very difficult, we are good friends off the court," Sinner said of the hard-hitting Darderi, who put up some late resistance.
Sinner told Margaret Court Arena, where temperatures hovered around 30 degrees in the early evening: "It was difficult to put the match away, happy I closed it in three sets."
Sinner sent down a bumper 19 aces in the match, and said his hard work had paid off.
"For sure, I feel more confident (on serve). Still room to improve, but happy how I have come back in the new season."
Sinner, 24, admits he struggles in the heat, and he dropped a set in his previous match, against Eliot Spizzirri of the United States.
But normal service resumed against Darderi, the 22nd seed, who was in the fourth round of a major for the first time.
The 23-year-old appeared overawed by the occasion, winning just nine points in falling 4-0 down in the first.
Sinner streaked ahead 5-0 in barely 20 minutes of one-sided action before Darderi got on the board.
It was only a temporary respite in the first match ever between the pair, Sinner sealing the set in 27 minutes.
Darderi made a better fist of the second set, winning his first service game, but was then broken as his frustrations boiled over.
He slammed his racquet to the floor and whacked a ball into the crowd, earning a warning from the chair umpire.
The third set was much closer, Sinner saving four break points in the ninth game, and the two exchanging heavy groundstrokes.
Sinner held for 5-4, and Darderi then saved two match points as he doggedly stayed alive and forced a tiebreak.
Darderi forged a 2-0 lead, then play was interrupted by a crying baby, and Sinner rattled off the next seven points without reply to finally break his opponent's resolve.