The wreck, which happened about 3 p.m. at Porter Lane and Ga. 53, involved a white Isuzu pickup and a tanker that authorities say was carrying 400 gallons of diesel fuel.
No fuel has spilled, but oil is leaking from the tanker where the bottom of the engine was ripped out.
Porter and Ga. 53 are closed in both directions, snarling traffic along the well-traveled corridor.
The situation and cleanup are being hampered by heavy rain that is moving across the area.
The impact killed the driver of the Isuzu, who Assistant Forsyth County Coroner Ted Scarborough has identified only as a 62-year-old Alpharetta man.
The driver of the tanker, whose name has not been released, was not injured.
According to witness accounts, the Isuzu was traveling west on Ga. 53 when it crossed the centerline and struck the tanker head on.