Two road trains collided and burst into flames on the Kamilaroi Highway, 100 kilometers east of Bourke, creating a path of destruction and field of debris.
At 7pm emergency services were called to a bridge on the western side of the town of Brewarrina, after the heavy vehicles crashed and caught fire.
Delays are expected throughout the day as the Kamilaroi Highway remains closed in both directions.
Both drivers died at the scene, with neither being identified yet.
Police said at this stage it is unknown what the road trains were carrying while firefighters continue working to control the blaze.
The Kamilaroi Highway will be closed for a few hours and is blocked in both directions.
Motorists are being urged to monitor the situation via live traffic updates.
Police say the circumstances surrounding the crash will be investigated and a report will be prepared for the Coroner.