Home favourite Antonelli, who was way down the order after a grid penalty, took advantage of a favourable strategy, an explosive new engine and a demonstration of passing excellence on Sunday, to become the first Italian in 60 years to win in Monza.
Charles Leclerc was earlier forced out of race after a 160-mph horror crash on lap two in what was a nightmare start for Ferrari in their home race.
Leclerc lost control of his car on the exit of the high-speed Curva Parabolica as he duelled with Australia's Oscar Piastri for fourth position.
The Monegasque flew through the gravel trap at the exit of the final corner before thudding into the tyre barrier and sustaining significant damage to his car at the end of the second lap.
McLaren driver Piastri was not affected by the incident and the 25-year-old Melburnian was able to continue after the re-start to eventually finish in fifth place.
"I think this weekend was definitely the strongest I've felt for a while, and my pace was the most encouraging it has been in some time," Piastri said.
"It was a good result for the team and probably the best result we could have got."
Antonelli crossed the line 3.8 seconds clear of Briton Russell to extend his lead from 59 points to 66 and follow in Ferrari's Ludovico Scarfiotti's footsteps as the first Italian to win at Monza's Temple of Speed since 1966.
"Oh my god ... it feels like a dream," Antonelli said after banking his seventh win of the season.
"It's unbelievable. I never would have believed I would be here today, but I am so happy."
Red Bull's Max Verstappen finished third, one place ahead of world champion Lando Norris.
Norris' fellow Brition, Lewis Hamilton, could only cross sixth behind Piastri to complete a poor day for Ferrari.
Despite his crash, Leclerc was able to remove himself from his stricken machine, but he was seen sitting on the grass in apparent pain.
Russell held his nerve at the restart following a 30-minute red-flag period after Leclerc's crash to keep clear of Pierre Gasly with Antonelli making up six places from 12th.
Russell soon had Verstappen for company and the Red Bull man streaked past his English rival for the lead on the 12th lap and by the start of the next lap, Antonelli had muscled his way up to third.
A boost came for Russell two laps later when he snatched the lead back from Verstappen. But Antonelli breezed past the Red Bull driver on the next lap and was in second and on lap 18, the Italian led the race after seeing off Russell on the long run down to the Variante del Rettifilo.
Over the next four laps, Antonelli and Russell traded positions four times for the lead before Russell got ahead of his team-mate on lap 23.
Antonelli was called in by Mercedes for a pit-stop and was 14 seconds behind when he left the pits. With 10 laps to go Russell's advantage had been trimmed to just five seconds.
The British driver was told to take "no risks" with his tyres with teammate in striking range.
Antonelli thought he lost his chance when he ran through the sand trap with four laps to go but he got his man the next time around to secure a stunning fightback win.
