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 Honda SUV, which was heading westbound on 50th Street, police said.
Police said both people on the motorcycle took out guns and fired shots at the SUV, 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.
Police said the SUV, left riddled with bullets, hit a parked vehicle before coming to a stop.
One neighbor, who did not want to be identified, saw two of the victims run away, adding that one of them asked for help.
"One of them, he just looked at me and said, 'Call the cops! Call the cops!' And then the other one, saw the other one running. Then, he was limping that way, and then he just dropped his phone right there because it had a bullet hole in it," the witness told ABC7.
That witness also told ABC7 that one of the victims cried out for his sister, saying she was shot.
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.
Police have not said whether the three victims are related or if anyone is in custody.
One woman who heard the gunshots spoke to ABC7 in Spanish, saying she is now afraid to come out of her home.
The witness who did not want to be identified told ABC7 they are "getting tired of all this, because all these gunshots is all you hear all the time."
Meanwhile, Area One detectives are investigating.
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