It happened just before 7 p.m. Tuesday in the 2800-block of South Ashland.
Police say Jason Kitchekeg, 26, and two others were writing graffiti on a wall when the victim started running. He somehow fell or jumped into the river and was in the water for about 30 minutes before he was pulled out. The incident occurred in an area of the South Branch of the Chicago River known as "Bubbly Creek."
The two people who were with Kitchekeg were taken into custody.
Kitchekeg was pronounced dead at 8:06 p.m. at John H. Stroger Hospital, according to the Cook County Medical Examiner's Office.
The Sun-Times Media Wire contributed to this report.