The new route is one of two the airline is introducing to the northern airport, with a second to Antwerp commencing on the same day.
The Antwerp connection will be operated twice daily during the week and daily at the weekend while the Ostend-Bruges service will be daily.
VLM Regional commercial director Konstantijn Huys said: "We are very happy to re-establish the route between Manchester and Antwerp.
"Antwerp is not only Europe’s second largest seaport and the world’s diamond capital, the city also has the second largest petrochemical cluster in the world after Houston, Texas.
"The city is also renowned for its thriving fashion, cultural, culinary and heritage scene.
"Passengers flying to Bruges-Ostend Airport are within 20 minutes of the medieval city centre of Bruges, also often referred to as the Venice of the North.
"Bruges-Ostend Airport is also the perfect gateway for a visit to Flanders Fields, where so many young people sacrificed their lives during World War One.
"In the lead up to November 11 there will be numerous centennial events in West-Flanders commemorating the end of the Great War."