The California Highway Patrol closed three northbound lanes near Terra Bella Street, where a car going against traffic crashed into oncoming vehicles.
Officials said firefighters and paramedics were sent to the scene at about 8 a.m. At least one person had to be extricated from a vehicle.
Authorities said four people were transported to area hospitals; three were in critical condition and one was in fair condition.
Traffic was held up until the wreck was cleared from the road and all lanes were reopened at about 9:15 a.m.
City News Service contributed to this report.