In Berlin alone more than 100,000 took to the capital's streets to urge Germany's leaders to immediately abolish nuclear power, police spokesman Jens Berger said.
Organizers said some 250,000 people marched at the "Fukushima Warns: Pull the Plug on all Nuclear Power Plants" rallies in the country's four largest cities, making them the biggest anti-nuclear protest in the country's history.
"We can no longer afford bearing the risk of a nuclear catastrophe," Germany's environmental lobby group BUND said.
The disaster at Japan's Fukushima Dai-ichi nuclear facility triggered Chancellor Angela Merkel's conservative government last week to order a temporary shutdown of seven of the country's older reactors pending thorough safety investigations. Officials have since hinted several of them might never go back into service.
Protesters shouted "Fukushima, Chernobyl: Too much is too much!" or "Switch them off," urging the government to shut down the country's 17 reactors for good. They also held a minute of silence to remember the victims of Japan's March 11 earthquake and tsunami.
In the northern port city of Hamburg some 40,000 turned out and more than 30,000 were on the streets in southern Munich, police said. Cologne police did not provide a figure and referred to the organizer's estimate of 40,000 protesters.
BUND, in turn, said some 120,000 turned out in Berlin, 50,000 in Hamburg and 40,000 in Cologne and Munich each.
Saturday's turnout easily topped rallies last April following safety incidents at a northern German nuclear power plant near Hamburg that had seen 140,000 people taking to the streets, BUND spokesman Thorben Becker said.
Nuclear power has been very unpopular in Germany ever since radioactivity from the 1986 Chernobyl disaster drifted across the country.
A centre-left government a decade ago penned a plan to abandon the technology for good by 2021, but Merkel's government last year amended it to extend the plants' lifetime by an average of 12 years. In a complete U-turn, the government has now put that plan on hold.
The cascade of failures at Japan's Fukushima plant has reignited the political debate on the use of nuclear power in Germany, Europe's biggest economy, and many opposition lawmakers have called to shut down all reactors even before 2020.
Germany, which stands alone among the world's leading industrialized nations in its determination to overcome nuclear power, currently gets some 23 per cent of its energy supply from its reactors, 17 per cent from renewable energies, 13 per cent from natural gas and more than 40 per cent from coal. The Environment Ministry maintains that renewable energy will be able to contribute 40 per cent of the country's overall electricity production in 10 years.