Police attended the M2, in Kent, just after 1pm on Christmas Eve after a collision between junction 5, for Sittingbourne, and 4, for Rainham.
It is believed a black Volkswagen T-Roc collided with the central reservation before overturning.
A woman in her 20s, who is yet to be named, was pronounced dead at the scene.
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A spokesperson for Kent Police said: “Witnesses including motorists with dashcam footage are being urged to come forward following a fatal collision on the M2.
“The incident happened shortly before 12.50pm on Christmas Eve, on the London-bound carriageway close to the Medway services (Junction 4).
“Officers from the Serious Collision Investigation Unit attended the incident and the carriageway was closed between Junctions 5 and 4 whilst initial enquiries were carried out.
“Anyone who witnessed the incident or saw the vehicle beforehand is urged to call the appeal line on 01622 798538 quoting reference BS/AW/092/25. Dashcam footage can also be uploaded online.”
A spokesperson for National Highways added: “The collision, reported to National Highways at 12:58pm is a single vehicle collision which has struck the central reservation barrier and has come to rest in an overturned position.
“Kent Police lead the response to this incident and the initial response this incident was supported by the South East Coast Ambulance Service and Kent Fire & Rescue Service.
“National Highways Traffic Officers are in attendance and have released the traffic that stationary within the closure.
“Due to the seriousness of the incident, Kent Police are carrying out detailed collision investigations at the scene.
“This process is essential to establish the circumstances of the incident, which means the closure is expected to remain in place throughout the afternoon.”