The man, of 23, is being questioned on suspicion of causing death by dangerous driving over the collision on the A500 at about 04:45 BST.
The two men who died, both aged 22, were from the north Staffordshire area, police said.
Part of the southbound carriageway was closed for seven hours after the crash at Cliffe Vale, a spokesman said.
The road has since reopened.
A West Midlands Ambulance Service spokesman said it quickly became apparent to crews arriving at the scene "that nothing could be done to save two men that were in the car". They were confirmed dead at the scene.
A third man "was treated for multiple minor injuries" and taken to Royal Stoke University Hospital.
Anyone with any information about the collision is urged to call police on 101.
A man has been arrested after two men died when a car and lorry crashed in Stoke-on-Trent.