Air ambulance staff were among those who rushed to the scene following the collision which happened last night in Marsh Lane near the junction with the A51 Lichfield Road in Whittington at about 10.20.
They were involved a collision with a white Vauxhall Vivaro resulting in the closure of the main road.
Staffordshire Police said both were this morning in a "critical, but stable condition" after suffering serious injuries.
The force also stated that the van driver remained at the scene and assisted officers with their inquiries over what exactly happened.
West Midlands Ambulance Service said the women were given advanced life support at the scene before being taken to hospital.
“Upon arrival at the scene we found two women who were pedestrians. They were assessed by ambulance staff at the scene and had sustained life-threatening injuries.
“We administered advanced life support and advanced trauma care to them at the scene. The two women were conveyed to Queen Elizabeth Hospital, in Birmingham, for further treatment.
“The driver - did not require treatment from ambulance staff,” ambulance service spokeswoman Shauna Farley said.
Three ambulances, two paramedic officers, a trauma doctor and critical care paramedic and the Midlands Air Ambulance Service critical care car attended.
The road was reopened at 3.45am on Tuesday.
The collision investigation unit has launched an appeal for witnesses or anyone who may have CCTV or dashcam footage of the area at the time to contact the team by phoning 101 quoting incident 913 of 29 May, or use Live Chat via staffordshire.police.uk website.