Speed was likely a factor in the crash, Illinois State Police said. A witness said the driver was going more than 150 miles per hour.
The crash occurred in the southbound lanes of I-57 at Flossmoor Road at about 8:53 p.m., police said.
The two men have been identified as Jacob Dochee, 45, of Frankfort and Samieh Jawdat, 26, of Crete.
Kelly Longmire was on the expressway when she saw the yellow Lamborghini speed past her.
"I was doing 80 so it was almost twice my speed," she said.
Seconds after the car sped past her, it crashed into a ditch.
Longmire and other drivers pulled over to help. Ten minutes later, the sister of one of the victims showed up screaming.
This morning, Longmire discovered that she knew Dochee, one of the victims. She had met him when he was building her ex-boyfriend's house in the city's Bronzeville neighborhood.
Longmire said Dochee was a father who will be missed in his community.
"He had many children and I can't imagine that they're not going to be asking 'where's my dad?' Longmire said.
Dochee was a prominent real estate developer who was also known as "Jacob Da Builder."
"Very disheartening to hear about the death of one of Chicago's visionaries Jacob Dochee. #Jacobdabuilder was a real estate developer and business man bringing a new face to entrepreneurship in #bronzeville. May we continue to be inspired by his narrative and legacy," a group called "Calling All Ancestors Project" posted on Facebook.
"My condolences to the family of Jacob Dochee who passed away yesterday evening. My prayers are with you," Ald. Sophia King (4th) said on Facebook.
All southbound lanes of I-57 were shut down while police investigated, but reopened Saturday morning. No other injuries were reported.
Sun-Times Media Wire contributed to this report.