Forest View police said officers responded to the scene near West 47th Street and South Central Avenue just after 1 a.m.
Responding officers found two damaged vehicles and a person lying on the ground nearby.
An off-duty emergency medical responder stopped to help provide aid, police said.
The victim was taken to a local hospital, where they were pronounced dead. Their identity was not immediately released.
What led up to the crash was not immediately clear.
Chopper 7 was over the scene, where investigators blocked traffic for several hours. One vehicle was seen being attached to a tow truck around 6 a.m.
Southbound Central Avenue was blocked from Pershing Road to 47th Street, and northbound Central was blocked from 47th to Interstate 55. The exit ramp to Central was also closed.
All roads have since reopened.
Authorities did not immediately provide further information.