A white Chevy Traverse was driving north at a high rate of speed just after 2:30 a.m. in the 1000-block of North Cicero Avenue, when it rear-ended an Acura MDX, CPD said.
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The impact caused the Acura to crash and then become engulfed in flames, police said.
The man driving the Acura was pronounced deceased by Chicago fire officials on the scene.
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The man driving the Chevy was taken to Mt. Sinai hospital in good condition, and will be issued traffic citations, CPD said.
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Major accidents is on the scene investigating.
Neither man was immediately identified.