The pedestrian was walking on the A442 Queensway in Stirchley, when the collision happened at about 1am.
Emergency services rushed to the scene after 999 calls.
West Midlands Ambulance Service said its staff arrived to find police giving first aid to the injured man.
A spokesman said: “The pedestrian was being given excellent first aid by police who were first on scene. He man sustained a serious injury which required specialist trauma care.
"Once stabilised the man was transferred on blue lights to Royal Stoke University Hospital for further treatment.”
As well as an ambulance, a paramedic officer and a MERIT trauma doctor and critical care paramedic attended the collision.