The public bus, thought to be carrying 15 passengers, flipped onto its roof upon impact. The vehicle had made a stop just before the accident, which happened around noon on the Landstraße route 414, some 50 kilometres north of Cologne.
“We still don't know why,” Radevormwald city spokesman Dietmar Rolf said.
Officials from the Oberbergisch county said eight people were injured, one seriously. The 45-year-old driver is thought to be among the dead.
Some 150 rescue workers and a helicopter are at the scene while divers are searching the river for victims. Many local residents rushed to the spot to watch their efforts.
“I came here immediately,” said one visibly upset woman. “I'm afraid my cousins were in the bus.”
A man that lives nearby said the stretch of road was known for been treacherous: “This is a dangerous road, especially around the bend and when it's wet.”
But Radevormwald Mayor Josef Korsten rejected implications that it was unsafe to drive. “I travel this stretch almost every day and I don't consider it dangerous when driving normally,” he said.