Police are appealing for witnesses to the terrifying incident in which the 27-year-old appeared to be driving eastbound, without any lights on, along the westbound carriageway of the A725 East Kilbride to Hamilton Road in High Blantyre, South Lanarkshire, on Wednesday night.
Her BMW 318 collided head on with a Ford Mondeo being driven by a 62-year-old man, before an HGV driven by a 42-year-old man crashed into the BMW on the carriageway at Hamilton Road.
Police were called out to the three-vehicle pile-up near the Hamilton Technology Park off-slip at around 9.40pm.
The woman was taken to Hairmyres Hospital in East Kilbride, where she later died.
The 62-year-old man was also taken to Hairmyres with minor injuries and was released after treatment.
The HGV driver was uninjured.
The road was closed for several hours with local diversions in place and was later reopened in the early hours of yesterday morning.
A report will be submitted to the procurator fiscal and inquiries are continuing in relation to the events leading up to the crash.
A police spokeswoman said the woman's family have been informed. Police do not intend to release her name.
It's the latest in a spate of accidents along that stretch of road.
A lorry driver died after his vehicle careered into a lamp post earlier this year in April.
Police have also received several complaints in the last year over youths throwing bricks and stones from the bridges over the dual carriageway.
Road policing officers have been out on extra patrols on the A725 bypass between Hamilton and Bellshill since March, following numerous incidents of dangerous driving, speeding and items being thrown from flyovers.
Witnesses to Wednesday's crash should contact Sergeant Scott Sutherland or Constable Joanne Johnson at the Divisional Road Policing Unit at Motherwell on 01698 483000.