Local media reported one train had derailed and several carriages overturned in the crash near Bad Aibling, about 60 kilometres south-east of Munich.
Rescuers have found the bodies of four people and 10 of the injured are in a very serious condition, police have said.
Teams were sent to the scene after the crash happened at 6:48am (local time) and helicopters and ambulances have been taking the injured to hospital.
“The current toll is four dead, 15 critically injured, 40 severely injured,” police spokesman Martin Winkler in the town of Rosenheim told AFP.
Regional rail company Meridian said in a statement that “a tragic accident occurred on the single-track route between Rosenheim and Holzkirchen”.
The regional police force in Upper Bavaria tweeted that several hundred emergency services workers were on the scene in the rural area.
The rail route was closed to traffic, as well as two local roads.