Police said the crash happened in the Lincoln Park neighborhood's 2200-block of North DuSable Lake Shore Drive just after 7:20 p.m.
A 20-year-old man on a motorcycle was heading northbound when he lost control and hit a barrier, police said.
Police said he then fell over the barrier and into a southbound lane, where another vehicle hit him.
The motorcyclist suffered multiple injuries to the body and was transported to Illinois Masonic Hospital, where he was later pronounced dead. His name was not immediately released.
CPD's Major Accidents Unit is investigating.