A 71-year-old man, who was the driver and single occupant of a red Hyundai, and a 79-year-old woman, who was the driver and single occupant of an orange Mini Cooper S were both pronounced deceased at the scene.
It happened at about 2pm on Saturday on the A518 Newport Road near to Aqualate, Coley, between Newport and Gnosall.
A spokesman for Staffordshire Police said: "Sadly, despite the best efforts of paramedics a man, aged 71, who was the driver and single occupant of the Hyundai, and a woman, aged 79, who was the driver and single occupant of the Mini, were both pronounced deceased at the scene.
"No other vehicles are believed to be involved at this stage.
"The families of both drivers are being supported by specialist officers at this time.
"A file will shortly be prepared for HM Coroner."
A spokesperson for West Midlands Ambulance Service said an ambulance, two paramedic officers and the Midlands Air Ambulance from Cosford attended the scene.
"On arrival we discovered two patients from the same car, a man and a woman," they said.
"Both patients were found in a critical condition and sadly, despite the best efforts of ambulance staff, it became apparent nothing could be done to save them and they were confirmed dead at the scene."
Anyone who was in the area at the time or may have any relevant dash cam footage is requested to contact Staffordshire Police on 101 quoting incident 363 of 23 April or e-mail the Collision Investigation Unit on CIU@staffordshire.police.uk