The 27-year-old American clinched her 52nd career win by finishing in an overall time of two minutes and 28 seconds, 0.48 secs ahead of Italy's Federica Brignone with Viktoria Rebensburg, of Germany, third in a time of 2:29.05.
The victory - only her second ever in the giant slalom - gave Vonn an unassailable lead over Slovenia's Tina Maze with five races left in the season.
Vonn's victory means she is the first American in history to win four overall World Cup crowns - in 2008, 2009, 2010 and now 2012 - moving her ahead of Phil Mahre who claimed three overall victories in the 1980s.
Olympic champion Rebensburg narrowly missed out on clinching the giant slalom title - a feat she would have achieved if she had finished second behind Vonn. Rebensburg is still likely to seal victory in the discipline at the final race of the season in Schladming.
Vonn, who lead after the first run, mastered the slope which was used in 2007's World Championships and raced into the lead after the first run.
Rebensburg was in second at the halfway stage but an impressive final run by Brignone pushed the 22-year-old into third.
"I don't know what to say," Vonn told ESPN after her fourth title was confirmed.
"I just wanted to have two aggressive runs today. I felt like I had nothing to lose and I was having fun. I'm just really excited, I'm thrilled. It's crazy."
Vonn has now surpassed Croatian Janica Kostelic, Swiss Vreni Schneider and Austrian Petra Kronberger, who all won three overall titles during their careers, but she still trails Austria's Annemarie Moser-Proell who has six World Cup titles to her name after dominating in the 1970s.
This year's overall win comes after Vonn missed out on claiming the title last year by the narrowest of margins, when she was beaten by German Maria Hoefl-Riesch by just three points.