Relentless Sinner sets up Australian Open blockbuster with Djokovic
The Italian second seed swatted aside the American eighth seed 6-3, 6-4, 6-4 and has dropped only one set in moving ominously into the last four.
The other semi-final at Melbourne Park is between world number one Carlos Alcaraz and third-ranked Alexander Zverev.
"We go day by day, today I felt I was moving again a little bit better, I feel physically stronger again," the relentless Sinner said after easing into a sixth consecutive Grand Slam semi-final.
"We all know what challenge I am up to," he said of facing Djokovic, 38.
"These are the moments you practise for and wake up for in the morning.
"It improves you as a player and a person, we are lucky to have Novak still here playing incredible tennis for his age."
Sinner and Shelton came into the quarter-final with the Italian having won eight of their nine previous meetings in straight sets.
The left-hander Shelton has got the better of Sinner just once, in their first encounter, in 2023.
Sinner's dominance includes winning their Melbourne semi-final 12 months ago, and it was to be more of the same on a cool evening on Rod Laver Arena.
Sinner raced into a 4-1 lead in the first set as he sent Shelton, who is a year younger at 23, scurrying to all corners of the court.
A Sinner ace sealed the first set in 49 minutes and, despite having the crowd willing him on, Shelton was broken again in falling two sets down.
Four-time major champion Sinner was imperious and looked unflustered on the few occasions that the aggressive Shelton put him under the cosh.
They went with serve in the third set and Shelton did his best to feed off what he has approvingly called a "rowdy" Melbourne crowd.
But he struck his 33rd unforced error to give Sinner three break points, and after saving one of them, the American double-faulted to gift his opponent a 5-4 lead and signal the end was close.
Djokovic, a record 10-time winner in Melbourne, took his place in the semi-finals when Italian opponent Lorenzo Musetti retired hurt.