The train strike was given the go-ahead on Tuesday after a labor court in Frankfurt rejected a temporary injunction sought by German rail operator Deutsche Bahn (DB).
During the strike, rail services will run on a heavily reduced emergency timetable, forcing many of DB's millions of passengers to cancel their journeys or find other ways of getting to their destinations. Some 80% of long-distance services will be canceled, while regional lines will be affected to varying extents, DB said.
Freight train drivers will also be striking until Friday evening.
The strike has been called by the train drivers' union, GDL, which is demanding better wages, along with a reduction in work from 38 down to 35 hours a week.
It is the third and largest strike by the drivers since their union took up negotiations with DB and other carriers in November.
Union vows strikes will continue
GDL chief Claus Weselsky told broadcaster ZDP on Wednesday that strikes would continue until his union's demands were met and that DB "must make offers that are substantial."
"If nothing comes by Friday, we'll take a break then go into the next labor dispute," he said, calling DB's latest offer "a provocation."
DB has proposed giving drivers various options on the number of hours they work. from 35 to 40 hours per week.