Authorities believe speeding played a role in the crash between a black Toyota sedan and a gray Scion SUV just after 8 p.m. in the 6300 block of Richmond Avenue near Greenridge Drive.
The black car was occupied by driver with no passengers, while the gray SUV had two adults in the front seat and two children in the backseat, police said.
When officials arrived at the scene, they reported finding both adults in the SUV dead.
Police believe the woman is the mother of the two children in the backseat, and the man is a relative. The two children, identified as a 5-year-old and a 10-year-old, suffered minor injuries.
Investigators are working to obtain video from nearby businesses while police talk to witnesses and look for family members who can care for the children.
Officials were still working to determine which driver was at fault. A DWI task force and crash reconstruction team were talking to the surviving driver, who was taken to the hospital.