'I got lucky' - Cramping Sinner drops set on way to Melbourne last 16
The two-time defending champion was broken three times in the first set and six times in total as he laboured to a 4-6, 6-3, 6-4, 6-4 victory on Rod Laver Arena over a lung-bursting 3hr 45min.
His reward is a clash next with fellow Italian Luciano Darderi, the 22nd seed.
With temperatures climbing to a forecast 40C, it was not the demolition job many predicted against a player ranked 85 with Sinner struggling to acclimatise in the brutal conditions.
Draping himself in ice towels during the changeovers, he suffered a fright in the third set with severe cramp that needed treatment.
Hobbling, he was only saved when play was halted due to the extreme heat and the stadium roof closed.
It was the first time Sinner had dropped a set in 12 matches, dating back to Vienna last year against Alexander Zverev.
"It was hot today, I started to cramp a little bit in the third set," he said. "And yeah, got lucky today.
"At the point when they closed the roof, it takes a little bit of time.
"I tried to loosen up a little bit. It helped. I changed a bit also the way of how I played certain points. That helped me today, for sure."
Sinner has a history of cramping in hot conditions.
He said he had no real explanation, but it could have something to do with not sleeping well.
"I feel like sometimes there are no real explanations. For example, last night I didn't slept the way I wanted to. The quality of sleep was not perfect. Maybe it was this, maybe not.
"Regardless, I try to be in the best possible shape every day. I know my body a little bit better now. I hope that it goes slowly away, which was the case today."
Sinner is striving to win three Melbourne titles in a row and join Novak Djokovic as the only men to do so in the Open era (since 1968).
He came out firing, breaking for 2-0 before letting his guard down to be broken back to love.
The Italian got in his groove and broke again with a searing forehand winner for 4-2, but once again was broken to love.
Struggling in the heat, he was broken for a third time to slide 5-4 behind with a composed Spizzirri serving out the set.
Incredibly, Spizzirri broke again for 1-0 in the second set, leaving Sinner shaking his head.
The world number two slowly began to figure out the American and broke back and held for 2-1, going on to take the set.
But the energy-sapping weather took its toll and he was left limping after a 20-shot rally in the third set.
Sinner was in real trouble and slumped 3-1 behind before the extreme heat rule was applied and he left the court while the roof was closing.
When they resumed, he broke straight away, looking more comfortable out of the sun's glare, with another break leaving him serving out for the set.
Unfazed, Spizzirri kept applying pressure and the pair exchanged breaks in the fourth set before Sinner finally seized control.