Chicago police said the crash happened near West 75th Street and South Vincennes Avenue in the Greater Grand Crossing neighborhood around 9:30 p.m.
A 37-year-old woman was driving a grey Buick sedan westbound when she tried to turn southbound and failed to yield at the intersection, police said.
The Buick then struck a black Dodge vehicle, which was traveling eastbound. An unoccupied, parked grey Mercedes sedan was also hit as a result of the crash.
Video from the scene captured extensive damage, with debris scattered everywhere. Witnesses said at least two people were ejected.
Two people inside the Dodge were taken to the University of Chicago Medical Center, where they were pronounced dead.
The Cook County Medical Examiner's Office identified them as 20-year-old Matthew Cuadra and 18-year-old April M. Valencia, both of Lansing.
Police said the Dodge's driver, a 26-year-old man, and two other passengers, a 15-year-old girl and a 25-year-old woman, were hospitalized with non-life-threatening injuries.
Officers issued the Buick's driver a citation for failure to yield during a left turn.
CPD's Major Accidents Unit is investigating.
Further information was not immediately available.