The evacuations began about an hour after the last car of an eight-car commuter train slipped off the tracks and material beneath the train caught fire, said Chicago Transit Authority President Frank Kruesi. The blaze filled the subway line with thick smoke and covered some commuters in soot.
Fire Department spokesman Larry Langford said at least 120 passengers were taken to hospitals, primarily for smoke inhalation.
Bomb and arson detectives were on the scene, but there was no evidence of foul play, Police Superintendent Philip Cline said.
Investigators were searching for the cause of the derailment and fire.
Service was shut down on a rail line that connects the city's West Side to O'Hare International Airport through downtown, said Chicago Transit Authority spokeswoman Ibis Antongiorgi.
Joel Johnson, 24, said he was on the train three cars from the back when "it felt like it jumped the line, and a fire started in the car behind me."
"People started running to the front. The whole place was filled with smoke," he said. "I could barely breathe."
Brenda Lopez, who was on the same car, said the train "dipped a little."
"I'm still kind of scared right now," she said. "You never expect it to happen on the train you're on."