Organisers said between 15,000 and 18,000 people took part in a rally at Opel's main German plant at Ruesselsheim, near Frankfurt, carrying banners proclaiming "Yes we can" and "Fighting back makes the difference."
"Opel must live," Foreign Minister Frank-Walter Steinmeier told the demonstrators, fearful for their livelihood as the beleaguered US parent company bids to slash thousands of jobs across Europe.
Steinmeier, a Social Democrat who will challenge Chancellor Angela Merkel in legislative elections in September, added: "Opel is not just about cars, it is about the people who go to the factory every day."
He said it was "unacceptable" and "disgraceful" that GM was not safeguarding their jobs.
Peter Giesser, a member of Opel's works council, said rallies were also expected at GM plants in Spain, Britain, Belgium and Poland.
In Sweden, employees at Saab, another GM subsidiary, were to stage a rally in the southwestern city of Trollhattan, location of Saab's main Swedish plant with 3,700 workers.
A works council member at an Austrian GM subsidiary, which employs 1,850 workers at a site near Vienna, called for a "European rescue plan" for GM companies, a call echoed by Steinmeier.
GM, which is still threatened with bankruptcy and on Thursday announced a $9.6 billion loss in the fourth quarter, has drawn up a European restructuring plan that would eliminate thousands of jobs.
The US firm has also said it wants to get rid of Saab, which currently benefits from a Swedish court ruling that has helped it to avoid going under. As for Opel, GM is mulling partnerships with outside investors or selling off stakes to keep the company going. In each case, the US group has appealed to public authorities in Europe for aid.
Merkel told reporters earlier Thursday that Germany wants to "build bridges" to help companies afflicted by the crisis and that the government's preferred method of support for Opel would be to provide loan guarantees. However, she warned that the government would not continue to finance companies with "structural weaknesses."
The demonstrators called for Opel to split from its parent company, carrying banners saying, "better without GM."
One employee, Marc Rost, who has worked for Opel for 18 years said the workers "want our bosses to see us as human beings ... not as machines that can be dismantled." Like his fellow marchers, Rost, 39, said he was scared that the site would close and he would lose his job.
"All this will no doubt end up in total chaos," Andy, a 20-year-old apprentice at Opel, told AFP.
Opel is set to hold a crunch meeting Friday to debate a restructuring plan, which German authorities have said is a pre-requisite for talks over aid. Germany's Economy Minister Karl-Theodor zu Guttenberg told a news conference he plans to speak to German regional leaders on Saturday about Opel's plight.
In a cruel twist of fate, Opel is actually increasing output because of strong demand for its compact models during hard times. The company said this week it has dropped plans for slowing production at its plant in the eastern city of Eisenach, which makes the Corsa model. Instead, it will now assign additional teams there.
Demand for the Corsa has also been boosted by a government €2,500-incentive scheme that encourages drivers to turn in old cars for new models that pollute less.
At the end of 2007, GM Europe employed more than 55,000 people, primarily in Belgium, Britain, Germany, Poland, Spain, and Sweden.