Racing in her fourth career downhill, the 22-year-old Olympic and world slalom champion finished in 1 minute, 27.55 seconds to edge Germany's Viktoria Rebensberg by 0.13 seconds.
"The biggest thing is I'm learning about the mentality to ski well in downhill and ski the way that I want to," said Shiffrin, third Friday in the opening downhill.
"I've skied here a couple times now, so I felt Lake Louise was a really good opportunity for me because I have some experience on the track. I wasn't planning to win, but I was planning to come here, do my best and see what happened."
The defending World Cup overall champion won a slalom last week in Vermont. She extended her overall lead over Rebensburg to 149 points. Rebensburg won the first two World Cup giant slalom races of the season.
"It's my first podium here and I don't know how many years I've been coming here now," Rebensburg said. "I was often pretty close to the podium, but today everything came together. Hopefully, I can win a downhill soon."
American Lindsey Vonn was 12th a day after crashing in the downhill opener.
"I think I had a hard time trusting my knee today," said Vonn, an 18-time winner at Lake Louise. "It's definitely pretty swollen and wasn't very happy with me. I'll go ice it now and hopefully it settles down a little bit more."
Shiffrin says she still thinks of Lake Louise as "Lake Lindsey."
"It's really cool for me to be here and experience what she's felt in past years," Shiffrin said.
The start was delayed 1 hour, 15 minutes because of a power outage after a power line to the resort failed.
"It was definitely weird, but I have to say huge props to Lake Louise for getting this race off," Vonn said. "They put in a major effort."
The course was shortened from Friday.
"Shortening the distance was definitely an advantage for me because it's flat on the top section and I'm not as good up there. From where we started today, it's fairly technical. I felt really good about that yesterday, so I took even more risk today and it paid off. I know that I was lucky with conditions yesterday and today, but I skied well and took some risk and it was really fun."
Switzerland's Michelle Gisin was third in 1:27.72. Austria's Cornelia Huetter was fourth after winning Friday.
American Stacey Cook was sixth.
A super-G is scheduled for Sunday.
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