The first flights took off on December 20th, with services set to run throughout the ski season until March 28th.
Commenting on the new flights, Mike Coombes, Air Southwest's deputy chief executive, said that Grenoble represented an excellent winter ski destination.
"Air Southwest is delighted that it can offer ski breaks for people from across the region right on their doorstep, without having to take a long road journey to fly from a distant airport," he said.
"Our new flights direct from Plymouth and Newquay have been extremely well received and this new service further demonstrates Air Southwest's commitment to Devon and Cornwall."
People wishing to book flights should visit the airline's website, with one-way tickets starting from £39.
Air Southwest announced last month that it had operated the first flight from the newly re-opened Newquay Airport.
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