The two-car crash happened at just before 10pm yesterday on Lichfield Road, just after the canal bridge and close to the junction with Lewis Grove.
Six people in total were injured. A driver was arrested after allegedly providing a positive breath test after the crash, police said.
Three ambulances, two paramedic officers and the MERIT Trauma Doctor and Critical Care Paramedic were sent to the scene.
A West Midlands Ambulance Service spokesman said: “On arrival, ambulance staff found two cars that had suffered significant damage.
“There were four people in the first car, two adults and two children.
"A teenage boy had suffered the most significant injuries. He was treated at the scene before being taken on blue lights to Birmingham Children’s Hospital with the doctor travelling with the crew.
“A younger boy also suffered potentially serious injuries and was taken to the same hospital with the critical care paramedic travelling with the second ambulance.
"The two adults in the car, a man and a woman, were assessed at the scene but had only minor injuries.
“There were two women in the other car. Both were treated for less serious injuries but were taken to New Cross Hospital for further assessment and treatment.”
A spokesman for West Midlands Police said: "Two children were injured in a collision on Lichfield Road, Wolverhampton around 10pm last night.
"Both were taken to hospital – a 14-year-old with a leg injury and a nine-year-old with a head injury. Their injuries are not deemed life threatening or life changing. Two other people in the same car received minor injuries.
"The driver of a Renault Clio was arrested after providing a positive breath test and was taken to hospital with a knee injury."