The accident happened in the town of Eberbach, which lies 33km northeast of Heidelberg. Children are believed to be among the casualties, police have confirmed. The five most seriously injured people could be in a life-threatening situation.
Police in Mannheim confirmed that the bus drove into the side of a house.
Three helicopters were being used in the rescue operation on Tuesday morning to take injured people to hospital.
Of the 47 injuries, 10 are said to be serious. The driver sustained light injuries.
The bus, which brings children from surrounding villages into the town each morning, drove out of its lane before colliding with several cars and finally crashing into the wall, police have said.
"The fully occupied school bus drove for reasons that were not immediately clear at full speed into several other vehicles and then into the wall of an electronics shop," police said in a statement.