Flybe is to add to its network from Southend operated by franchise partner Stobart Air with a route to Maastricht.
Flights to the Dutch airport start on July 10 and follow Ryanair withdrawing a Stansted-Maastricht service.
Flybe will serve the route six days a week and aims to carry up to 25,000 passengers in its first year, rising to 80,000 in three years.
Fares have gone on sale starting at €34.99 including taxes and charges.
Maastricht Aachen airport chief executive Sander Heijmans said: “The fact that Flybe will operate non-stop flights from Maastricht to London Southend is very welcome news.
“To have the biggest European regional carrier as a new customer for the airport is a significant development that fits in our strategy to offer air connections not only to the leisure passenger but also to our business community.
“The frequencies offered, combined with the fast connection between London Southend and the city, make this a very good way to travel to London.
“And for travellers from the UK, this new route offers an excellent start of a city-trip to Maastricht and surroundings.”