One boat sank in the horror collision, which took place in the Moabi Regional Park about 290 miles east of Los Angeles, on Saturday night around 8pm local time.
Victims were swept five miles down river following the smash.
San Bernardino County Fire District spokesman Eric Sherwin said the missing people are “presumed submerged”.
Emergency services scrambled to the scene, with one person suffering life-threatening injuries airlifted to a Las Vegas hospital.
Six other people were rushed to local hospitals with less serious injuries and another six sustained minor injuries.
Several victims are thought to have been hurled into the water by the force of the collision.
Other passengers are believed to have jumped into the water and been carried down river.
Mr Sherwin said: “We had victims of this collision that were located three to five miles downstream from the original point of impact.”
The area was crowded with people enjoying the US Labor Day weekend at the time of the crash.
Rescuers abandoned the search until Sunday morning because of the danger to divers working in the fast-flowing water after dark.
Underwater sonar images of the submerged boat did not appear to show the two missing passengers, according to the local fire department.
The second boat was badly damaged, but remained afloat.
Other recreational boats raced to the scene to rescue victims.
The Moabi Regional Park is a popular water recreation area along the California border with Arizona.