Milk spilt across the motorway after the crash which happened in the southbound carriageway between Junction 7 for Great Barr and Junction 6 Spaghetti Junction at around 5.45am and saw lanes shut in both directions.
A van driver and car driver, both men, were seriously hurt and taken to hospital while a third patient was treated and discharged at the scene.
There were delays of more than an hour for southbound drivers throughout rush hour as a result, with traffic backed up eight miles past the M54 at Junction 10a.
All lanes were reopened at 9.20am.
National Highways regional operations manager, Adam Morgan said: “The M6 southbound is now back open following an incident this morning which involved seven vehicles.
"We worked with the emergency services to manage traffic while they were at scene and we also dealt with a spillage of milk on the road.
"While congestion eases, we’d encourage motorists to leave additional time for their journeys this morning.”
All drivers remained at the scene and were spoken to by police officers but nobody was arrested, West Midlands Police said.
A West Midlands Ambulance Service spokeswoman said two ambulances and a paramedic officer were sent to the scene along with police and highways officers.
“Upon arrival crews found three patients," they said.
“The first, a man who was the driver of a van. He was assessed and had sustained potentially serious injuries that were not believed to be life threatening. He received treatment from ambulance staff at the scene.
“The second, a man who was the driver of one of the cars. He had sustained potentially serious injuries that were not believed to be life threatening. He received treatment on scene.
“Both men were conveyed to Heartlands Hospital for further treatment.
“A third patient was assessed by ambulance staff, they received self care advice and were discharged at the scene.
“No further patients required treatment.”
A spokeswoman for West Midlands Police said: "We were called to a crash involving a number of vehicles, including a lorry carrying milk, between junctions 6 and 7 of the M6 at about 5.40am today (Thursday).
"Two people were taken to hospital with injuries which are not believed to be life-changing.
"All drivers involved remained at the scene and were spoken to by officers, who also helped with traffic management until the vehicles were cleared at just before 8am."