Police said the shooting happened in the Back of the Yards neighborhood's 1700-block of West 50th Street around 3:30 p.m.
The motorcyclists pulled up to a car, which was traveling westbound on 50th Street, police said.
Police said both people on the motorcycle took out guns and fired shots at the car, hitting a 26-year-old woman, an 18-year-old man, and a 16-year-old boy.
One neighbor told ABC7 they saw multiple people running away after several shots were fired back-to-back.
More than 10 gunshots can be heard on one neighbor's surveillance video.
Shortly after, people can be seen running, with one person yelling that they were shot.
Police said the car hit a parked vehicle before coming to a stop.
The 26-year-old woman, shot in the back, was transported to the University of Chicago Medical Center, where she was pronounced dead.
The 16-year-old boy, shot in the arm and leg, was taken to the same hospital in critical condition.
The 18-year-old man, shot in the hip, was transported to the same hospital in serious condition.
Area One detectives are investigating.
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