Officers responded to the eastbound lanes of I-290 at Canal Street at around 1:30 p.m.
A Chicago Fire Department spokesperson says the victim was transported to Stroger Hospital where he was pronounced dead.
The Cook County medical examiner's office identified the victim as Nshaune Johnson. An autopsy ruled his death a homicide.
Preliminary information indicates shots were fired from an unknown vehicle, also traveling near Canal Street, police said.
All of the eastbound lanes near Canal were closed for roughly four hours while police investigated.
The shooting remains under investigation and no further information is available at this time, police said.
Anyone with information is asked to contact ISP at 847-294-4400.
In 2019, The Illinois State Police responded to investigate 52 expressway shootings on the Chicagoland expressways in Cook County.
ISP said there have been 112 shootings this year, including Friday's incident.