The student-organized "March For Our Lives" is to feature rallies from coast to coast, with the main event scheduled to take place in Washington within sight of the US Capitol.
"The kids are leading the movement," said Democratic Senator Chris Murphy of Connecticut, where 20 children aged six and seven years old were killed in December 2012 at Sandy Hook Elementary School.
Students from Marjory Stoneman Douglas High School in Parkland, Florida -- where 17 people were shot dead on February 14 by a 19-year-old former classmate -- have been the driving force behind the march.
With a mixture of outrage and passion, they have been relentlessly badgering US lawmakers to enact a ban on assault rifles and to expand background checks to cover all gun purchases, even private sales.
"The march is just the start," said Aalayah Eastmond, a 17-year-old junior who took shelter beneath the body of a classmate during the Stoneman Douglas shooting.
"Columbine happened -- nothing's changed. Sandy Hook happened -- nothing's changed. Parkland happened -- nothing's changed," Eastmond said.
"We will fight for this until change happens," she said at an event with members of US Congress.
Since the Parkland shooting, the state of Florida and the US Congress have made only modest tweaks to gun laws and President Donald Trump's proposal to arm teachers has been met with widespread resistance.
Organizers say more than 800 marches are being held across the country and around the world under the slogan #NeverAgain, with the Washington event alone anticipated to attract at least 500,000 people.
The protests are expected to be the largest for gun control in the United States -- which has more than 30,000 gun-related deaths a year -- since the Million Mom March in May 2000.
The appeals for stricter gun regulations have drawn the backing of Democratic lawmakers, and a slew of American celebrities have pledged $500,000 donations to support the protests.
Performing at the rally in Washington are Lin-Manuel Miranda, Ben Platt, Ariana Grande, Jennifer Hudson, Miley Cyrus, Demi Lovato, Common, Andra Day and Vic Mensa.
The marchers have also attracted the support of former president Barack Obama, who tried but failed to reform gun laws following the Sandy Hook slaughter.
Former president Billl Clinton said America "owes its gratitude to the students of Stoneman Douglas and their peers across the country who have joined their cause."
Murphy, the Connecticut senator, told AFP the student-led movement needs to become an "electoral force, and this march may be the beginning of that."
Conscious of their growing political power, March For Our Lives organizers provided a link on their website for supporters to register to vote.
They have also called on supporters to vote against lawmakers who receive money from the National Rifle Association, the powerful US gun lobby that fiercely defends the Second Amendment's "right to bear arms."
"Either you stand with the kids or you stand with the NRA," said David Hogg, a Stoneman Douglas student.
Meanwhile, Lyft, the ride-hailing service, said it would offer free rides to 50 marches around the United States. Several restaurants in Washington said they would hand out free lunches to high school students.
Robert Kraft, the owner of the New England Patriots, sent the American football team's plane to Parkland to fly the families of the 17 people killed at Stoneman Douglas to Washington along with injured students.
According to a Quinnipiac University poll, 63 percent of American voters approve of the march in support of tougher gun laws but are not optimistic it will lead to new legislation.
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