Odermatt, the reigning World Cup champion and current leader, finished 0.20 seconds ahead of Norwegian veteran Henrik Kristoffersen (28) and 0.92 in front of Olympic silver medallist Zan Kranjec (30).
"It was probably the biggest struggle of my life," said Odermatt, who has now won three of four giant slaloms this season.
"Difficult, hard, exhausting," he added. "After already a week in Val Gardena and then coming here - two races in a row, four very difficult courses, and a lot of turns."
Odermatt maintained his lead on the first descent during a wild second run down the 'Gran Risa', in which he made a series of recoveries after bouncing off the racing line several times.
"It was a big improvement from yesterday. I was awake today," said the Swiss after a dominant first run.
The next men's event is a night slalom in Madonna di Campiglio on Thursday, although Odermatt is not competing in the slalom as he will return to Switzerland for a Christmas break.