At about 5.24pm, police were called to a two-vehicle collision on the A23 at Bolney.
A black Nissan Qashqai had collided with a white Volkswagen Crafter on the southbound carriageway, causing the Qashqai to spin and overturn off the nearside carriageway, according to police.
A police spokesman said: “The Nissan driver, a 61-year-old woman from Brighton, was taken to Royal Sussex County Hospital in Brighton with serious head injuries, where she remains at this stage. The VW driver was uninjured.
“The road was closed for several hours while emergency services dealt with the incident.”
Anyone who saw what happened – in particular anyone who has dash cam footage of the incident – is asked to report it online at https://www.sussex.police.uk/rtcappealresponse or phone 101, quoting Operation Share.