Two children riding in the pickup were taken to the hospital with minor injuries. The other four passengers were unhurt, troopers said.
The crash happened just after 8 p.m. Friday near Dunes City, about 8 miles south of Florence.
Oregon State Police said Brittany Alexander, 23, of Custer, Wash. was driving her Chevrolet Spark north on Hwy 101 when for some reason she crossed into the southbound lane near milepost 198.
Alexander hit a Dodge Ram pickup truck towing a box trailer south on the highway. Officials pronounced her dead at the scene.
Guillermo Trujillo, 52, of Happy Valley, was driving the pickup with five passengers at the time of the crash. Police officials said that two of the children riding in the car were taken to Peace harbor Hospital with minor injuries. Trujillo, an adult female passenger and two other children in the truck were unhurt in the crash, state police reported.
The roadway was blocked for over two hours while crews worked to clean up the crash.