It happened on the 3300 block of S. 61st Street when police say the driver of a Chevy Tahoe flipped over and landed onto a black Hyundai.
Police say seven people were ejected from the Tahoe.
The male driver, roughly in his 30s, was pronounced dead at the scene, police say. The female passenger of the Tahoe also died.
Five children, ages 8 to 14 were also inside the Tahoe and thrown from the vehicle. Police say four of the children suffered minor to moderate injuries. One of the children may have suffered major injuries, said police.
The driver and two passengers of the Hyundai were all taken to an area hospital for minor injuries.
Police are still investigating the cause of the crash.