The shooting was reported about 2 a.m. near Ranchero Road, a spokesperson for the California Highway Patrol said.
According to investigators, a person or persons in a red vehicle opened fire on a gray vehicle with four people inside, striking two of them.
The injured were transported to a hospital and are expected to survive, the CHP said.
No one was in custody in connection with the shooting, and a detailed description of the red vehicle was not available.
The CHP announced the lane closure on X, formerly known as Twitter, shortly after 6:30 a.m. near Oak Hill road.
The southbound side of the freeway was unaffected by the closure.
As the morning commute got underway, northbound traffic was backed up at the scene and drivers were being diverted at Mariposa Road.
Just before 9 a.m., the Highway Patrol announced that all lanes were open.
The possible motive for the shooting is under investigation.