The victims were traveling in a Nissan sedan southbound in the 3000-block of DuSable Lake Shore Drive at about 8:48 p.m. when police said they were hit by a Chevy sedan changing lanes.
The Nissan sedan then lost control and struck a tree, police said.
The man driving the Nissan and a woman passenger were transported to the University of Chicago Medical Center, where they were pronounced dead, police said.
Two 21-year-old women passengers in the Nissan were transported to Northwestern Memorial Hospital in critical condition, police said.
The man driving the Chevy and a woman passenger were transported to Stroger Hospital in fair condition, police said.
The CPD Major Accidents Unit is investigating the crash.