The bus came to a screeching halt after police say the driver of a black SUV crashed into the double decker.
"The driver of this Ford Explorer made a sudden turn in front of the bus, cutting the bus half off and the driver applied the brakes and of course we had impact to the bus and the vehicle," SFPD Sgt. Frank Harrell said.
The Embarcadero lit up as police and medics quickly arrived. Only passengers on the bottom level of the bus were hurt.
People rushed out of restaurants to find out what was going on. "There were a lot of police cars, a lot of ambulances, people being taken away on the stretchers and being put into ambulances," witness Amy Van Artsdalen said.
Some passengers were treated immediately on the sidewalk before being taken to three separate San Francisco hospitals.
The majority of the victims suffered minor injuries and the most severe injury was a broken ankle.
The driver of the Big Bus and the driver of the SUV were tested for drugs and alcohol and both passed.
Big Bus' general manager says the tour company's driver has a solid record. "Our driver is fine, a little shaken up. Been with us for quite a long time, a senior driver," Andrew Smith said.
The driver of the SUV will be cited for making an unsafe lane change.