Prema duo Piastri and Logan Sargeant were level on points heading into the season finale with ART Grand Prix's Theo Pourchaire in third place, nine points adrift of the leading pair in the drivers' championship.
There was drama on the opening lap as Sebastian Fernandez attempted to drive around the outside of Red Bull junior Lawson at the San Donato right-hander on the opening lap.
ART GP's Fernandez was pushed wide and re-joined the track three-wide with title hopeful Sargeant and Trident's Lirim Zendeli.
Sargeant and Zendeli collided and both drivers were sent into the gravel and out of the race on the entry to the Luco left-hander, leaving Pourchaire as Piastri's only obstacle to the FIA F3 crown.
The safety car was required to recover the stricken cars and it was Piastri who dropped from seventh to 10th place while Pourchaire climbed from eighth to sixth place.
Pourchaire charged through to third place, making overtakes on his teammates Alexander Smolyar and Fernandez as well as Ferrari junior Enzo Fittipaldi.
19-year-old Piastri responded by overtaking the ailing Smolyar and his Prema team-mate Frederik Vesti to move into eighth place.
Pourchaire was unable to make significant progress towards second-place runner David Beckmann (Trident), who he needed to overhaul to beat Piastri on countback.
Hitech GP's Lawson dominated at the front of the field for his third race victory of the season, almost eight seconds ahead of Beckmann, who registered his sixth podium of the year.
Pourchaire was forced to settle for the final place on the podium in third place while Piastri pipped Pourchaire's team-mate Fernandez in a photo finish for seventh place.
This was enough for Piastri to seal the FIA F3 title, three points ahead of Pourchaire and four points clear of his teammate Sargeant.
HWA Racelab's Fittipaldi earned his best result in the series in fourth place ahead of the 2019 Macau Grand Prix winner Richard Verschoor (MP Motorsport) and his HWA team-mate Jake Hughes - making his last appearance in F3 after five years.
Piastri was seventh ahead of Fernandez, Saturday's race winner Frederik Vesti and the third ART of Smolyar.
|3||Theo Pourchaire||ART Grand Prix||21||36'39.572||9.193||1.387||180.341||10|
|4||Enzo Fittipaldi||HWA AG||21||36'40.778||10.399||1.206||180.242||8|
|5||Richard Verschoor||MP Motorsport||21||36'41.361||10.982||0.583||180.194||6|
|6||Jake Hughes||HWA AG||21||36'42.815||12.436||1.454||180.075||5|
|7||Oscar Piastri||Prema Powerteam||21||36'43.900||13.521||1.085||179.986||4|
|8||Sebastian Fernandez||ART Grand Prix||21||36'43.943||13.564||0.043||179.983||3|
|9||Frederik Vesti||Prema Powerteam||21||36'45.359||14.980||1.416||179.867||2|
|10||Alexander Smolyar||ART Grand Prix||21||36'49.779||19.400||4.420||179.508||1|
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