Emergency services attended the scene of the two car road traffic collision, and the road was closed with drivers advised to find alternative routes.
Three ambulances and a paramedic officer attended, treating three patients for injuries that are not believed to be serious.
Staffordshire Fire and Rescue had crews from Stafford, Risingbrook and Cannock at the scene, and said on arrival they found a black Peugeot 107 and red Vauxhall Corsa involved in the collision, with the Corsa on its roof.
Crews used hydraulic cutting equipment to extricate the driver and a passenger from the Corsa.
A woman in her 60s, and male passenger in his 80s were extricated from the car and taken to hospital.
Staffordshire fire and rescue service said in a statement: "Fire crews have rescued two people from a car involved in a collision in Penkridge.
"Firefighters were called to Teddesley Road, at 8.45am this morning (Monday 15 August), following reports of a two-vehicle-collision.
"Crews from Rising Brook and Stafford attended as did paramedics and Staffordshire Police.
"On arrival, crews found a black Peugeot 107 and a red Vauxhall Corsa involved in a collision, with the Corsa on its roof.
"Crews used hydraulic cutting equipment to extricate the driver of the Corsa, a woman in her 60s, and a male passenger, in his 80s, from the car.
"Both were taken to hospital by land ambulance.
"Crews remain at the scene."
A spokesperson for West Midlands Ambulance Service said in a statement: “We were called at 8:40am to reports of a two car RTC on Teddesley Road. We currently have three ambulances and a paramedic officer at the scene treating three patients for injuries not believed to be serious.”