The incident began when the driver of a pickup truck, Lance Hopper, 27, of Cleveland veered from the westbound lane on the highway and crashed into vehicles stopped at the traffic light heading eastbound.
After Hopper's truck collided with the first vehicle on the inside lane, five other vehicles ended up pushing and crashing into each other.
Cleveland Police Chief Buster Bingham said Hopper was given a blood test and the department is awaiting the results.
The accident remains under investigation.
"This was a substantial accident. As long as I've been here, I can't remember a six-vehicle crash," said Bingham.
Bingham added that a number of people were seriously injured but only one was airlifted to the MED in Memphis to receive further treatment for their injuries.
Skid marks, debris and vehicle fluids covered the area and five of the six vehicles involved were towed.
Authorities closed Highway 8 and the entrance to nearby Cotton Row to cleanup and investigate the scene.
Along with the CPD, the Cleveland Volunteer Fire Department and the Bolivar County Sheriff's Department also responded.
"We just ask that everyone pay close attention while they are driving," added Bingham. "Safety can come into play with so many situations — whether it's texting and driving, drinking and driving or just focusing on the road.
"Traffic accidents lead to serious injuries and sometimes death. Everyone knows the guidelines for safe driving and people need to take heed to the warnings."