The crash happened on the A38 near the Clay Mills junction, Burton upon Trent, Staffs, on Friday afternoon.
Police said the lorry collided with a Clio which then crashed through the central reservation, hitting another car travelling the opposite direction.
The two girls who died were from the Burton upon Trent area but have not been named.
Two adults females were treated for their injuries at the scene.
Police arrested the driver of the lorry, who was from the Telford area in Shropshire.
'Crossed reservation'
A spokesman from Staffordshire Police said: "A Volvo articulated large goods vehicle being driven by a male from the Telford area was in collision with a Renault Clio driven by a woman from the Burton upon Trent area.
"These two vehicles were travelling on the southbound carriageway.
"As a result of this collision the Clio crossed over the central reservation and collided with a Mercedes Benz car travelling on the northbound carriageway.
"Two teenage female passengers from the Renault Clio are dead as a result of this incident."
Police are appealing for any witnesses to come forward.
In a separate incident on the same day, a man died after getting trapped in a burning car following a head-on collision with a lorry in the Staffordshire Moorlands.
The ambulance service described the scene near the Winking Man pub on the A53 in Upper Hulme as "horrific".
The driver of the lorry, which also caught fire, was taken to hospital in Macclesfield with minor injuries.
Police have not released the name of the dead man.
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