The 25-year-old used his huge serve and forehand to great effect once again to claim his fifth career title and become the first Italian champion at the prestigious event.
Berrettini banged down his 19th ace as he served for the match and claimed victory on his first match point.
The world No. 9 did not drop serve since the first round and held 46 service games in a row.
World No. 41 Norrie dug deep to take the match to a deciding set but faltered at 3-4 in the deciding set as he became Berrettini's third British victim of the week after defeating five-time champion Andy Murray and Dan Evans on his way to the final on his tournament debut.
Norrie dropped serve with a double fault in the six game of the opening set to hand Berrettini the momentum.
Berrettini was close to winning in straight sets when he had break points at 4-4 in the second but Norrie hit back superbly to even up the match by winning the tiebreak.
It was only a temporary hiccup for Berrettini, however, as he powered through the decider to become the first debutant to win the title at Queen's Club since Boris Becker in 1985.
Becker went on to win Wimbledon a few weeks later and Berrettini will head to the All England Club with high hopes of a deep run.