The collision happened on Interstate 40 in New Mexico, near the Arizona border.
Early reports from the scene indicate the truck blew a tire, sending it into oncoming traffic.
It smashed into the front of the passenger bus, which had 48 passengers on board.
Many of those on the bus were sent to hospitals.
Nine bus passengers were being treated at University of New Mexico Hospital with three more patients expected to be transported there later on Thursday.
No details about the patients’ conditions were released, nor was there confirmation of the total number of injured.
Initial investigations shows that a semi-truck was travelling eastbound on I40 when it blew out a tire. The semi-truck then lost control, a police spokesman said, before confirming the truck and bus collided head-on.
Video from the scene showing the aftermath shows the trailer of the truck overturned, the crumpled bus and debris across the floor.
The semi had ripped open and partially collapsed, with its cargo spilling out.
The vehicles are on what appears to be a grassy verge, suggesting the collision pushed them off the road.
A large number of emergency services staff can be seen in attendance. One worker carries a spinal board.
Passing motorist Eric Huff told reporters the semi’s trailer was upside down and shredded to pieces, and the front of the Greyhound bus was smashed, with many of the seats pressed together.
Part of the side of the bus was torn off, he said.
Truck driver Santos Soto III saw people crying on the side of the road.
I was really traumatised myself, because I’ve been driving about two years and I had never seen anything like that before, Soto said.
#NMSP officers have confirmed at least 4 fatalities from the bus at this time. Many bus passengers were transported with serious injuries. The exact number of injuries is still being investigated. This scene remains active and updated information will be posted here.
I’m a pretty strong person and I broke down and cried for at least 30 minutes, he added.
Chris Jones saw the wreckage and stopped to help.
He says he came across the driver of the semi sitting on the shoulder of the highway and that the driver told him that one of his front tires had burst, forcing the truck to veer into oncoming traffic, where it struck the bus.
Greyhound said the bus was heading from Albuquerque to Phoenix.
We are fully cooperating with local authorities and will also complete an investigation of our own, a Greyhound spokeswoman said.
The westbound lanes of the interstate closed as a result of the crash.
News Source SkyNews