Investigators remain of the scene of the shooting which happened around 2:30 a.m.
A blue Honda Accord carrying four people was heading southbound on Highway 101 near Candlestick Park just south of the Tunnel Avenue Exit, when a vehicle pulled up next to it and opened fire.
The driver was shot twice and remains in critical condition. Two passengers in the backseat were both hit in the leg. One person riding in the passenger seat was not hit. Officials say the shooting victims are expected to survive.
Southbound 101 was closed for more than two hours while authorities searched the area for evidence.
A Brisbane Police Sergeant told ABC7 they did not yet know what prompted the shooting.
The California Highway Patrol talked to the one uninjured passenger but details of that interview have not been released.
The incident is still under investigation.
