The Austrian took Olympic gold in this discipline at the Winter Games in Sochi earlier this year, but was only joint fifth in the World Cup standings at the end of 2013-14.
Mayer suffered a setback in October when he sustained a medial ligament tear and bruised his spine in a fall during giant slalom training.
That injury ruled him out of the Giant Slalom World Cup opener in Solden, as well as the second meeting in Finland earlier this month.
But the 24-year-old makes his return in the downhill at Lake Louise this weekend after making a full recovery from his injury.
"I am pain free and therefore start with nothing in the way," he said.
"I am very pleased with the healing and I am glad that it is now finally starting for me."
One man who will not be present in Canada is double reigning downhill champion Aksel Lund Svindal, who tore his Achilles while playing football last month.
The Norwegian took the crown by 210 points last time out, ahead of Hannes Reichelt, who was forced to miss the final months of the previous campaign - including the Olympics - with a herniated disc in his back.
Also down to feature at Lake Louise will be Italy's Christof Innerhofer, who took silver behind Mayer in Sochi.
Innerhofer, who also claimed bronze in the combined event, missed the meeting in Solden with a troublesome back problem, and the 29-year-old concedes his preparation has been less than ideal.
"My form is not optimal," he said. "My inflammation still bothers me. I hope that it will be better in the next few days."
Another man who hopes to overcome injury and compete in the event is Ted Ligety, who remains a doubt after have surgery on a dislocated left wrist sustained in training last week.
Also looking to get his downhill season off to a winning start will be Kjetil Jansrud, who won bronze at the Winter Games and finished fourth in the overall World Cup standings.