The student-led protests – called March For Our Lives – have grown out of a movement calling for change after 17 people were killed by a gunman at a high school in Florida last month.
Half a million people are expected to descend on the march in Washington DC.
More than 800 sister protests are planned nationwide and abroad.
Solidarity marches have taken place in London, Edinburgh, Geneva and Sydney.
Organisers have said it may become “standing room only” for the main event in Washington, as the swelling crowds could make it hard to move. The march there was to begin at 12:00 local time (16:00 GMT).
Participants want to seize on public outrage in the wake of the 14 February massacre at Marjory Stoneman Douglas High School in Parkland to convince US politicians to finally take decisive action, including by banning the sale of assault weapons.
However, the issue divides Americans. The right to bear arms is protected under the 2nd amendment of the US constitution and the National Rifle Association (NRA) gun lobby remains highly influential.
President Donald Trump is at his Mar-a-Lago resort in Florida for the weekend.
On Saturday afternoon, the White House released a statement praising the “many courageous young Americans exercising their First Amendment rights today”.
It also cited steps it is taking to tackle gun violence, including banning bump stocks, plus enacting the STOP School Violence Act, which seeks to improve school security and increase training for students, staff and local law enforcement.
There are also plans to improve criminal background records so gun buyers are properly vetted before making a purchase.
Organisers say up to half a million people could rally in Washington DC, which would make it the largest protest since last year’s women’s march. The singer Ariana Grande and Lin-Manuel Miranda, the man behind hit musical Hamilton, are set to perform. (Courtesy BBC)