Before the tournament, 25-year-old Cecchinato had failed to win a match in his previous four appearances at a Grand Slam tournament.
But he has cut a swathe through the lower half of the men’s draw beating 10th seed Pablo Carreno Busta in the third round, the eighth seed David Goffin in the last 16 and the 2016 winner in the quarter-final.
In a nailbiting fourth set tiebreak, Cecchinato staved off three set points and was unable to capitalise on three match points. But serving on the fourth match point, Djokovic fired to the Italian's backhand and the return flew past the onrushing Serb to clinch the shootout 13 points to 11.
"Maybe I'm sleeping,” he beamed after the victory. “It's amazing, it's unbelievable for me. I'm very happy because it's unbelievable to beat Novak Djokovic in a quarter-final at Roland Garros. It's amazing.”
He is the first Italian to reach the last four at a Slam since Corrado Barazzutti at Roland Garros in 1978 and he is the lowest placed man in the semi-finals in Paris since 100th-ranked Andrei Medvedev in 1999.
Cecchinato will next play the seventh seed Dominic Thiem after the Austrian routed the second seed Alex Zverev 6-4 6-2 6-1.