Five people were sent to local hospitals with immediate life-threatening injuries, according to San Jose Fire, and 13 people were treated for minor injuries.
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California Highway Patrol said it will take about six to eight hours to clear the scene.
The accident is under investigation and prosecutors have been notified, which Miceli said is a routine measure.
Miceli said the driver will be asked to submit a blood sample to test for alcohol and drugs.
The driver has cooperated with investigators, according to Miceli.
Two women passengers were killed, Miceli said.
Officials say the bus appears to have been the only vehicle involved.
Representatives for Greyhound could not be immediately reached for comment, but spokeswoman Lanesha Gipson told the San Francisco Chronicle newspaper that the bus company was fully cooperating with authorities.
The accident happened just after 6:30 am, northbound on the 101 near Highway 85, according to California Highway Patrol (CHP).
Alex Ehlers tells KCBS that he could feel the bus weaving and the driver jerking the wheel.
Final passenger update: 9 injured/transported, 2 deceased, 9 waiting transport to San Jose Greyhound station.
“He stated that he did feel worn out and that he did get some coffee in Gilroy when he dropped off two passengers”, CHP Officer Chris Miceli said. The bus carrying the driver and 19 passengers flipped onto the center divider, fire Capt. Christopher Salcido said.
Traffic was already snarled due to rainy conditions, but the accident had cars stopped along the northbound section of Highway 101 for several miles.
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CHP hasn’t released the identity of the victims.
