The accident occurred at around 3 p.m. ET and involved at least six other vehicles.
The Ontario Provincial Police say that a vehicle lost control on the Highway 6 bypass and struck a transport truck. Four other vehicles were involved in the accident.
The woman and little boy were pronounced dead on the scene.
There have been no reports of other serious injuries.
The OPP have shut down Highway 6 in Caledonia until further notice.