Ontario Provincial Police said the accident involving a CP Rail freight train occurred at a level crossing outside the town of Lakeshore, where police said the family is from.
Police identified the dead children as Wynter Williams, 6, and her sister, Brooklyn, 3.
Their brother, Dryden Williams, 4, was taken to a Detroit hospital with serious, life-threatening injuries, police said in a news release.
The childrens' father, Andrew Williams, was in a Windsor hospital with serious, life-threatening injuries. The youngest passenger, one-year-old Jasmyn Williams, received minor injuries.
Police Const. Stephanie Moniz said the crossing doesn't have many safeguards.
"There's no monitoring at this intersection," she said.
"There's no bar that comes down, there's no flashing lights. It's simply a sign with the railway 'X' on it, along with a warning sign that says 'stop before' or 'check both ways before crossing,'" she said.
Visibility was good at the crossing, which intersected a gravel road, and the crew tried to alert the van's driver said CP Rail spokesman Kevin Hrysak.
”The crew did everything within their means to alert the driver of the oncoming train by sounding off their whistle and then eventually putting the train in an emergency brake application,” said Hrysak, who added it would be up to police to reveal more details on the circumstances surrounding the collision.
The crew was relieved of duty and was offered critical stress counselling, said Hrysak.
“In this tragic situation, definitely can have a dramatic impact on the crews in that regard because they are the first ones on the scene,” he said.
CP Rail police were working with provincial police to determine why the crash occurred.