Australia's flying kangaroo airline will operate services between Bendigo and Sydney.
Qantas' Q300 turboprop aircraft touched down at Bendigo Airport on Monday, ahead of its inaugural return service, operating six days a week from March 31.
It is expected to attract almost 15,000 visitors to the regional centre each year, Treasurer Tim Pallas said.
"This landmark deal will create local jobs, boost tourism and create enormous opportunities for local businesses in Bendigo," Mr Pallas said.
The service will create 25 jobs and pour $2.8 million into the local economy in the first year, the state government says.
It comes after the airport was given a $15 million upgrade - using local, state and federal money - after years of lobbying to improve the digs.
Labor MP for Bendigo West Maree Edwards labelled it a "historic day".
"It's a big vote of confidence in everything Bendigo has to offer and proof there's no place in regional Victoria quite like it," she added.
© AAP 2018