Brignone was celebrating her first World Cup win and ninth podium finish after edging out Olympic slalom champion Shiffrin and Tina Weirather with a combined time of 2:24.27 minutes.
Much of that was owed to the first run where Brignone posted the only sub 1:11.00 time, coming in almost a second ahead of Shiffrin.
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And while the American was a tenth of a second quicker on the second run, Brignone's 1:14.16 was still enough for her take the win – in doing so becoming the first Italian to win a women's giant slalom event since Denise Karbon in January 2008.
Shiffrin was 0.85 seconds back in second with Weirather a further half a second back, just edging out Switzerland's Lara Gut when it came to the final podium place.
Britain's Alex Tilley was 23rd after the first run but her chances of placing highly were ended after she failed to finish the second run.
Run 1 - Run 2 - Overall
1. Federica Brignone (Italy) 1:10.11 1:14.16 2:24.27
2. Mikaela Shiffrin (U.S.) 1:11.06 1:14.06 2:25.12
3. Tina Weirather (Liechtenstein) 1:11.53 1:13.99 2:25.52
4. Lara Gut (Switzerland) 1:11.62 1:14.04 2:25.66
5. Tessa Worley (France) 1:12.19 1:13.80 2:25.99
6. Viktoria Rebensburg (Germany) 1:13.07 1:13.48 2:26.55
7. Sara Hector (Sweden) 1:11.64 1:15.04 2:26.68
8. Eva-Maria Brem (Austria) 1:12.41 1:14.74 2:27.15
9. Irene Curtoni (Italy) 1:12.03 1:15.14 2:27.17
10. Frida Hansdotter (Sweden) 1:13.47 1:13.82 2:27.29