The pedestrian is 12 years old and currently is in an induced coma and in critical condition, CHP Officer Sam Morgan said.
Morgan said the boy, who is from Oakland, was reported on eastbound Highway 580 near Fruitvale Avenue shortly after 6:25 a.m. when he was hit.
The incident initially prompted the closure of all eastbound lanes on Highway 580, but all lanes reopened as of about 7:45 a.m., according to the CHP.
Morgan said the boy was hit by at least one car.
He said traffic came to a stop but a second collision occurred when a driver who wasn't paying attention struck several other cars.
Two people were treated for minor injuries and pain from the crash, Morgan said.
Morgan said it doesn't appear that the driver who struck the boy did anything wrong.
He said the incident was "a very tragic situation" and the boy may have been disoriented.
Oakland police Sgt. Arturo Bautista confirmed that the boy had been reported missing but said he did not immediately have any additional details about him.