Defending champion Kjetil Jansrud of Norway was third, 0.18 seconds behind Mayer, on another near-perfect clear and cold day for Alpine racing. It is Jansrud's fifth career Olympic medal after getting downhill silver.
Norway had won the past four Olympic men's super-G races — a streak begun at the 2002 Salt Lake City Olympics.
Aksel Lund Svindal, the 2010 Olympic champion in super-G, placed fifth the day after taking Mayer's downhill title.
"Unbelievable," said Mayer, adding that he grew up admiring the Olympic silver medal that his father, Helmut Mayer, won in the super-G at the 1988 Games in Calgary.
Mayer's week begins with crash
It's been an up-and-down week for Mayer. He crashed into a course-side television cameraman Tuesday in the slalom leg of the combined event, won by his teammate, Marcel Hirscher.
He was still feeling the effects of that fall two days later, with a disappointing ninth-place finish when he attempted to defend his 2014 Olympic downhill title.
"I didn't know if I would start the downhill," the 27-year-old Austrian said. "I had real pain in my hip."
Still, Mayer has a history of recovering from severe injury since his first Olympic gold. He broke two vertebrae in his back in a crash at a World Cup downhill at Val Gardena, Italy in 2015. He underwent surgery and spent 11 days in a hospital before slowly making his way back to training.
The last non-Norwegian to win the men's super-G gold medal was Hermann Maier at the 1998 Nagano Olympics. The Austrian great won that race three days after walking away unhurt from a spectacular cartwheeling crash in downhill.
VIDEO | Canada's Dustin Cook grabs top-10 finish
Dustin Cook of Lac-Sainte-Marie, Que., was the top Canadian in ninth place with a time of 1:25.23.
Manuel Osborne-Paradis of Invermere, B.C., was 22nd in 1:26.39. Broderick Thompson of Whistler, B.C., was 23rd in 1:26.45 and Toronto's Jack Crawford skied off course early and didn't finish.
The super-G, short for super-giant slalom, is a single run raced on a slightly shorter, twistier course than downhill and is more unpredictable. The skiers do not get to practice through the exact set of gates designed by a national team coach who is chosen by lottery.
An Italian coach set Friday's 2.3-kilometre course, though that didn't help his racer Peter Fill, the No. 1 starter. Fill missed a gate after taking the wrong launch angle over a jump.
Two pre-race medal contenders lost speed by striking the same flagged gate with their right arms. Hannes Reichelt of Austria was knocked off balance, and Aleksander Aamodt Kilde of Norway had his ski pole ripped out of his right hand.