Police responded to a call at 4:38 p.m. from the bank at 211 Airport Blvd., Sgt. Joni Lee said.
A man had approached a teller and handed over a note saying he would "blow the teller's head off," Lee said, although no gun was visible.
The teller gave the suspect an undisclosed amount of money, and he fled the scene in a dark-colored Toyota 4Runner, according to Lee.
South San Francisco police set up a county-wide roadblock to apprehend the suspect, but the attempt was unsuccessful.
The roadblock was canceled after about 20 minutes, and the investigation was ongoing tonight.
The suspect was described as a black man wearing a New York Yankees hat, a Yankees jacket, blue jeans and a black hooded sweatshirt.