A California Highway Patrol spokesperson said the suspects started driving the wrong way when they entered the 10 Freeway near the Kellogg Drive off-ramp.
The driver lost control, hit a dirt berm and rolled over onto a transition road of the 71 Freeway, CHP said.
Two suspects were ejected from the car and pronounced dead at the scene. Two others inside the car ran away but were later taken into custody.
Authorities said the chase began on the 71 Freeway in Pomona and went through freeways and surface streets.
It's unclear what prompted the pursuit.