The driver of the white BMW sedan was shot east of Baldwin Park Boulevard just after midnight. The car crashed into the center divider following the shooting.
When the California Highway Patrol arrived on scene, they thought it was a typical traffic accident.
"When they approached, they saw that the driver had blood on him, and also there was blood on the vehicle," said CHP officer Edmund Zorrillo.
The driver, a man in his 20s, was taken to Los Angeles County-USC Medical Center for emergency surgery for multiple gunshot wounds. He is in critical but stable condition.
"We don't know what motivated (the shooting) as of yet," said CHP Officer Kerri Rivas. "When the victim comes conscious, investigators will be asking him questions."
A 23-year-old female passenger was not hurt, and even tried to save the driver in the moments after the crash by getting out of the car and flagging down help.
It's unclear who fired the shots and a suspect description was not available.
The westbound lanes of the 10 Freeway were shut down for several hours. Lanes reopened about 5 a.m., just before the morning rush hour.
Anyone with information was urged to call the CHP Baldwin Park Station at (626) 338-1168.