The CPD Marine Unit arrived to the scene at about 3:00 a.m. on West 129th Place near Halstead Street, police said.
The car was found partially submerged in the Little Calumet River, in the West Pullman neighborhood.
A 30-year-old man exited the car after the crash, but when police arrived he was dead in the water.
A woman, 30, was also in the vehicle. Police said she exited the vehicle before the car went into the river. She was sent to the hospital with non-life threatening injuries.
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No other details were provided.