Police say the car was heading southbound when it struck the median, overturned and flipped into the northbound lanes.
The car then struck another car that was northbound.
It happened early Tuesday morning near West 94th Street.
The victims have not been identified.
The accident is under investigation, but officials believe speed may have been a factor.
The northbound West Side Highway was shut down north of 79th Street as police investigated and crews worked to clear the wreckage.
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