Police said the crash happened in the 1700-block of East 103rd Street just before 12:20 a.m.
A gray sedan was traveling eastbound on 103rd Street when its driver rear-ended a semi, which was traveling in the same direction.
The sedan's driver was pronounced dead on the scene.
The semi's driver was not injured.
Area Two detectives are investigating. Police did not immediately provide further information about the crash.