The GDL union called on its members to walk out from 3:00 pm (1300 GMT) today on freight services and from 2:00 am (0000 GMT) on Saturday on long-distance and regional passenger services.
The stoppages -- on traditionally one of the busiest weekends in the autumn because of a school holiday -- would last until 4:00 am (0200 GMT) on Monday, GDL said.
The union accused national rail operator Deutsche Bahn of stone-walling in talks over its demands for a five-percent wage hike and a shorter working week of 37 hours.
"With its 50-hour strike on a holiday weekend, GDL and its chairman Claus Weselsky has lost all sense of proportion," the company said in a statement.
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"GDL is running amok," it added, pointing out that the autumn school holidays began or ended this weekend for 11 of Germany's 16 regional states.
Deutsche Bahn pledged to "do everything to keep disruptions to a minimum" and said it would deploy additional staff at stations and on trains to ensure at least one-third of services will run.
The magnitude of the industrial action was surprising in a country where warning strikes rarely last more than a day. The last time Deutsche Bahn was hit by an industrial dispute as serious as this was in 2007-2008.
Berlin is working on legislation to stop small groups of employees from paralysing large parts of the country's infrastructure, such as rail and air travel, after several airline strikes. A draft law is expected in November.
GDL accused management of issuing "nice-sounding statements with no substance".
The union also wants to represent other groups of employees within Deutsche Bahn, not just the drivers, but conductors, catering staff, dispatchers and other staff as well, a demand which management rejects.