The fourth seed showed patience and resilience to claim a 6-4, 7-6(5), 6-3 win against the Russian who now owns the ugly record of 10 defeats out of 10 in Grand Slam quarter-finals.
Sinner, who beat world number one Djokovic twice at the end of 2023, has reached the semi-finals without dropping a set.
Fifth seed Rublev, as he always does, threw the kitchen sink at his opponent but was left with the same old sinking feeling as he consistently failed to take his chances, especially when leading the second set tiebreak 5-1.
That proved pivotal as Sinner hit back in majestic fashion to take the second set and from that moment on the outcome never looked in doubt.
The Russian wore a world-weary expression in the third set and dropped serve to hand Sinner a 4-2 lead and the clean-hitting Italian duly closed out a comfortable win at nearly 1.30am local time to reach his first Australian Open semi-final.
Sinner will take heart for his forthcoming battle with 10-time champion Djokovic on Friday having beaten him at the ATP Finals and in the Davis Cup Finals in November.
"I'm really lucky to be facing the world number one in the semi-finals," Sinner, who lost to Djokovic at Wimbledon last year in his maiden Grand Slam semi-final, said on court.
"It's going to be tough but the only thing I can control is that I'll fight 100% for every ball and see what happens."
With the day session extending late into the evening, Sinner and Rublev did not even start on Rod Laver Arena until 10.45pm local time.
It was hardly ideal, but Sinner will be relieved that he managed to finish the match relatively quickly as a result of his incredible ability to fend off break points.
He brushed off the opening set in 38 minutes as Rublev, whose game is almost identical to Sinner's, made too many unforced errors.
The second set was a different story though with Rublev putting Sinner under immense pressure with his explosive hitting. Rublev had break points in the fourth, sixth and eighth games but each time Sinner slammed the door shut.
Sinner has now saved 26 of the 28 break points he has faced in his romp through the draw.
The Italian clutched his stomach at times during the second set but later explained it was not an injury but because he felt gassy. When Rublev then took a stranglehold of the breaker, thumping a 148kph forehand to lead 5-1, Sinner was in trouble.
But there was no panic and any discomfort he was feeling was not visible as he roared back to deliver a gut punch to Rublev and snatch the second set.
After that, it was all too familiar for Rublev as yet another chance to reach a Grand Slam semi-final was snatched away.
"It was really tight but these are the moments I love to play," Sinner said. "This is what I practice for and I'm really excited when we always have these pressure points.
"I'm just really trying to stay aggressive and it went my way today."
