Gaia town hall said traffic restrictions would come into force at 8am on Friday and remain in place until Sunday evening.
The aerial acrobatic competition involves planes flying through and round obstacles moored in the river and the circuit is between the Luiz I and Arrábida bridges meaning many roads will be cut to traffic.
The Red Bull Air Race first came to Portugal in 2007 on the River Douro and the mayor of Gaia expects more than a million spectators over the two days of the event (Saturday and Sunday).