Mancuso, whose best finish this season in any event was 12th, clocked 1 minute, 38.87 seconds down the sunny Olympia delle Tofane course.
Johanna Schnarf of Italy was second, 0.06 seconds behind, and overall leader Maria Hoefl-Riesch of Germany was third, 0.29 behind.
"I felt like I had a good run," Mancuso said. "It wasn't perfect everywhere, but I was really going for it."
Mancuso has always saved her best skiing for the Olympics. She won gold in giant slalom at the 2006 Turin Games and took silver in downhill and super-combined at the 2010 Vancouver Games.
"Definitely my confidence is getting better and better," she said.
The Cortina schedule calls for super-G races on Thursday and Sunday and downhill races Friday and Saturday.
Two of the races were originally scheduled for Cortina last weekend but got wiped out by heavy snowfall. The other races were moved from Garmisch-Partenkirchen, due to a lack of snow in the German resort.
Apart from World Cup finals, skiers rarely face four races in four days. Even at the Olympics and world championships, there are days off between races.
"That's not a problem for me since I'm doing all events. I'm used skiing every day," Hoefl-Riesch said. "Of course four days in a row is a tough schedule. But it shouldn't be a problem."
However, there is a possibility of more bad weather in the coming days.
"I hope that there's not so much snow coming again, because the slope is really good right now. It's perfect," Hoefl-Riesch said. "It would be great to have nice and fair races."
Hoefl-Riesch has two career wins in Cortina and seven podiums.
Mancuso won a super-G in Cortina in 2007 and has six second-place finishes on the Tofane course. But she hasn't won a race since a parallel slalom in Moscow two years ago, and she feels her equipment has been a big reason.
"Even though we've had canceled races I've been spending a lot of times on my boots (free) skiing," Mancuso said. "That's the most important thing for me—to feel really comfortable and confident on my equipment. ... I've put in the hours I needed."
With the U.S. team set to name its Sochi squad on Sunday, two other Americans also fared well. Stacey Cook was sixth and 21-year-old Jacqueline Wiles was 12th.
The Sochi Games open Feb. 7 and Mancuso's preparation over the past few days has included a lot of mental training, visualizing the course and "just focusing on really good skiing."
"I'm sure if I'm skiing well then the results will come," she said. "And it doesn't even matter what place I end up in the races going into it. Even today having a really good training run that's a really good confidence (booster) for me."
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