Exeter is regaining four domestic routes lost through the collapse of Flybe in March 2020.
Loganair has stepped in to revive flights to Newcastle, Glasgow and Edinburgh.
A fourth route to Norwich, originally planned for September, has been brought forward to July 12 in what the airline described as a sign of rising confidence in domestic aviation as the UK comes increasingly out of Covid-19 lockdown.
The routes will be flown by 49-seat Embraer 145 regional jets.
More: Loganair unveils plans to increase services to Scottish islands
Loganair plans Norwich-Exeter service as ex-Flybe routes are restored
Glasgow will Initially be served twice a week on Mondays and Fridays, rising to four flights a week from May 31 and a daily service from July 5.
Edinburgh will be flown five times a week, rising to daily from June 21.
A twice a week Newcastle link doubles from May 24 before going daily from July 5.
Norwich will see four flights a week starting on July 12.
Fares on the Newcastle, Glasgow and Edinburgh services start at £59.99 one-way, with Norwich at £49.99.
Chief commercial officer Kay Ryan said: “I know many of our customers have been waiting for Newcastle, Edinburgh and Glasgow services to resume, and we are also very pleased to be able to add Norwich to our Exeter roster earlier than planned.
“Bookings from all four of Loganair’s partner airports are proving very popular to this great part of the country.
“Importantly, these services fill gaps left by the collapse of Flybe, with almost every domestic destination from Exeter now being restored by Loganair and other carriers over the coming months.”
Head of sales and revenue Donna McHugh added: “It’s great to have taken our first flight from Scotland to Exeter, and we are very much looking forward to developing our relationship with business and leisure travellers and agencies in the south-west.”
Exeter airport operations director Stephen Wiltshire said: “The recommencement of domestic air connectivity between the south-west, north-east, and Scotland is a milestone moment for Exeter airport.
“The long-awaited return to flying is wonderful news for business and leisure passengers, giving a boost to the regional economy and enabling holidaymakers to take welcome ‘staycation’ breaks in Devon, Newcastle, Glasgow, and Edinburgh – some of the UK’s most popular destinations.”
More: Loganair unveils plans to increase services to Scottish islands
Loganair plans Norwich-Exeter service as ex-Flybe routes are restored