A major redevelopment of the stadium ahead of Euro 2016 has increased the capacity to 67,000 - but has come at a considerable cost.
OM have now failed to reach an agreement with officials in Marseille over the increase in rent, and the opening home fixture against Montpellier on August 17 will now be played at the Stade de la Mosson.
"After the most recent negotiations to reach an agreement on the rental tariff of the Stade Velodrome broke down with the Marseille town hall, the Olympique de Marseille directors announce that OM will not play in Marseille," read a statement on the club's official website.
"The first home match of the season, against Montpellier on the weekend of 15-17 August, will be played at the Stade de la Mosson.
"Olympique de Marseille, once again, apologises to its supporters."
Marseille's second home game of the season against Nice is due to be played on August 29 but it is unclear whether negotiations with officials will continue over the Stade Velodrome.
"The club tried everything possible to ensure the Marseille fans could support their team at the Stade Velodrome," said OM general manager Philippe Perez.
"But the municipality's radical stance has left us no other choice but to make this difficult decision.
"Unfortunately, it is the only option open to preserving the club's interests.
"There is no way OM could afford to pay the tariff demanded by the town hall."