The Austrian, who also won the Olympic super-G in Sochi, won the race despite finishing seventh in the first run.
Her combined time of 2 minutes, 26.39 seconds was 0.21 faster than surprise runner-up Anemone Marmottan of France. Lara Gut of Switzerland and Eva-Maria Brem of Austria tied for third, trailing Fenninger by 0.39.
Hoefl-Riesch placed 21st in what is typically her weakest discipline and earned only 10 World Cup race points.
Fenninger's 100 points brought her within 67 of the 2011 overall champion from Germany with six races remaining this season.
Congratulating Fenninger in a post on her Twitter account, Hoefl-Riesch wrote: "Now you are the favourite for the big crystal globe."
In her past four races, Fenninger has collected two Olympics medals, finished second in a World Cup downhill and now taken her sixth career World Cup win.
The 24-year-old Austrian's second GS victory this season lifted her to second behind Jessica Lindell-Vikarby of Sweden in the season-long discipline standings.
Lindell-Vikarby placed sixth in front of her home crowd, 0.82 behind, and has a 54-point lead over Fenninger.
Are hosts another giant slalom on Friday, after Thursday's race was a replacement for one canceled last month in Kranjska Gora, Slovenia.
Tina Maze of Slovenia, the Olympic champion in GS, held a clear first-leg lead Thursday but had a strangely cautious second run to fall to fifth place.
Marmottan and Brem both recorded their first career podium finishes in the World Cup.
Mikaela Shiffrin of the United States placed 15th, 2.16 behind Fenninger. The Olympic champion in slalom will get a chance to race her favorite event on Saturday.
The season concludes next week with the World Cup finals races in Lenzerheide, Switzerland, where weather has been a major factor.
Hoefl-Riesch clinched her 2011 title by only three points from Lindsey Vonn when the final GS race was canceled, and last year none of the men's and women's downhill and super-G races were completed.