Chopper 7 was over the scene at 9 a.m., showing the damage left after a car crashed head-on with a semi, officials said.
The sheriff's office said the people who died were in the car that crashed into the semi.
A third vehicle was also struck about 7:50 a.m.
Police said a 2009 Acura sedan, driven by a 51-year-old man of Stoughton, Wisconsin, was traveling east on Route 173, when it drifted into the westbound lane.
A 45-year-old Stoughton, Wisconsin woman also died.
The driver of the third vehicle, a 54-year-old Salem, Wisconsin woman, suffered non-life-threatening injuries.
The crash shut down Route 173 between Kilbourne Road and U.S. 41 in both directions.
No other information was available.