Emergency crews are at scene, along Highway 144, between Sainte-Basil in Edmundston and the village of Rivière-Verte.
No one was injured.
Officials do not believe the train was carrying any dangerous goods, based on the manifest, said city spokesperson Mychèle Poitras.
It appears most of the cars were carrying wood and paper products, and automobiles, she said in a statement.
It's unclear how many cars derailed.
Motorists are being asked to avoid the area. A section of Highway 144, between Exist 26 and Smyth Street is closed to traffic.
CN officials and representatives from the Department of Environment are on site, along with members of the Edmundston Police Force, Edmundston Fire Department and ambulance services.
The derailment occurred at about 3 p.m.
The train was from Moncton and was travelling westbound.