Tens of thousands gathered in Hibiya park in central Tokyo, where activists and unionists packed a concert hall to voice their opposition.
Scholars, business people and volunteers gave anti-nuclear talks as musicians performed, before the crowds marched through the government district of Kasumigaseki to parliament.
They planned to hand petitions to anti-nuclear lawmakers, urging the government to stop its nuclear programmes.
"I think it is adults' responsibility to achieve zero nuclear power, before we die" said one of many banners held by the marchers.
"Sayonara, nuclear power," another sign said.
Similar rallies were held elsewhere in Tokyo and across the rest of the nation, with local media reporting as many as 150 anti-nuclear events planned for the weekend and on Monday.
Protesters are calling for Prime Minister Shinzo Abe, who took office late December following his party's election win, to dismantle all nuclear plants.
Public opposition to nuclear power peaked after a 9.0-magnitude earthquake struck Pacific waters in northeastern Japan on March 11, 2011, and unleashed a massive killer tsunami which battered Fukushima Daiichi nuclear plant.
The plant was hit by a meltdown and explosions that severely contaminated the vast farming region and became the worst nuclear accident in a generation.
Japan turned off its stable 50 reactors in the wake of the disaster, but restarted two of them citing possible summertime power shortages.
Abe, whose conservative Liberal Democratic Party has close ties with the nation's powerful business circle, has repeatedly said he would allow reactor restarts if their safety could be ensured.
In many tsunami-hit cities residents dressed in black Sunday for ceremonies to mourn the victims of the disasters, which killed 15,881 people while 2,668 remain unaccounted for.
In the hard-hit city of Rikuzentakata, where almost 1,600 people died and 217 people are still missing, mayor Futoshi Toba reiterated his pledge to rebuild the city.
"We will move forward to build a beautiful city that is the pride of the nation where its citizens live happily and comfortably," he said.