The accident occurred on State Road 59, north of Brazil, in an area just south of Christ Community Church around 10:30 a.m.
Clay County Sheriff Mike Heaton released preliminary information that indicated investigators believe the accident was caused when a northbound passenger vehicle crossed the double yellow line into southbound traffic, striking a Dodge Big Horn 4X4 edition pick up truck pulling a utility trailer head on.
The impact bent the frame of the pick up truck and forced the car's engine to be thrown into a nearby creek.
Due to the severity of the accident, both drivers, whose names will not be released until officials contact their respective families, were temporarily trapped inside their vehicles.
At the scene, Heaton said the full extent of the victims' injuries was unclear, but both were awake and talking with medical personnel before being transported.
The female driver of the passenger vehicle was airlifted from the scene to Wishard Hospital in Indianapolis by Air Evac, while the male driver of the truck was transported by TransCare Ambulance to Terre Haute Union Hospital.
While both lanes of the highway were temporarily closed while the accident debris was removed, the highway was reopened around 12:30 p.m.
Members of Brazil City Fire Department, Clay County Sheriff's Department, Clay County Search and Rescue and Dick Johnson Volunteer Fire Department responded to the scene.