It happened on Highway 6 near Briar Forest, just blocks away from Westside High School, around 11:40 p.m. Sunday.
Three vehicles were involved.
According to police who looked at security video from a gas station, the wrong-way driver was in a white Ford Crown Victoria northbound on Highway 6 when he began to lose control in the intersection.
He veered into the southbound lanes of the highway after passing Briar Forest, driving in the wrong direction.
He tried to correct his mistake, but a black Mercedes struck him on the driver's side, police said.
While that was happening, a third vehicle, a gold Toyota, hit the Mercedes.
The driver of the Crown Victoria and a passenger in the Mercedes died at the scene, police said, adding two other people in the Mercedes were taken to the hospital.
"We don't believe intoxication is going to play a part for the driver that caused the secondary crash. We don't know about the first," Sgt. Dallas with the Houston Police Department said.
The northbound lanes of Highway 6 were shut down, but reopened Monday morning shortly after 6 a.m.
Police are in the process of contacting the families of those who were killed.
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