The accident happened shortly after 11:30 a.m. on U.S. Route 20 just west of Wakeman.
The women were the driver and passenger of a Honda Accord that was traveling eastbound when the driver, Evelyn Edler, 68, of Wakeman, drifted left of center and struck the tractor-trailer, which was westbound, according to Sgt. James Faunda of the Ohio Highway Patrol.
The tractor-trailer attempted to get out of the way, but the car hit the side of the trailer, sustaining severe damage.
Edler and passenger Ann Hoover, 62, of Wakeman, were flown to St. Vincent Mercy Medical Center in Toledo. Edler was listed in serious condition this morning, and Hoover was listed in fair condition. The driver of the semi, a man from Parma, refused treatment.
Wakeman Fire Chief Jim Tansey said firefighters used the Jaws of Life to remove the women from the car.
Route 20 was shut down for at least an hour, and traffic was backed up after that.