The star joined forces with her cousin, Senator Charles Schumer, to unveil a set of proposals for more stringent background checks on gun buyers.
"The time is now for American people to rally for these changes," she said.
President Obama recently said the failure to pass gun safety laws was the greatest frustration of his presidency.
His comments came on 23 July, just hours before a gunman opened fire on a movie theatre in Lafayette, Louisiana, killing two women and injuring nine other patrons, before taking his own life.
John Houser, 59, legally purchased his semi-automatic 40-calibre handgun in Alabama in 2014, following a background check that failed to reveal he had a history of psychiatric problems and had been the subject of domestic violence complaints.
Schumer, whose film was playing at the cinema, said the incident sickened her.
"I've thought about these victims each day since the tragedy," she said at a news conference at the senator's office in New York.
"People say, 'Well, you're never going to be able to stop crazy people from doing crazy things,' but they're wrong. There is a way to stop them," she added.
Senator Schumer, a New York democrat, wants to improve background checks by creating financial incentives for states that submit information to a database the FBI uses to screen gun buyers.
His bill would also create penalties for states that fail to submit records to the database. He stressed that the proposals were about strengthening the background check system, not putting new restrictions on buyers.
He also urged Congress to provide full funding to the Substance Abuse and Mental Health Services Administration, which faces a proposed 4.4% cut of $159m (Â£101m).
But with gun ownership a contentious issue in US politics, the senator acknowledged he would struggle to get his bill passed into law.
"We're up against a powerful lobby, so having people like Amy - who people respect and listen to - is a great antidote," he said. "She reaches people that, frankly, I would never reach."
Schumer, who is known for her raunchy, no-holds-barred sketch show on Comedy Central, said she expected backlash for speaking out about guns, but would not back down.
"I'll handle it the way I've handled it the last 10 years," she said. "I've had death threats and a lot of hate directed toward me. But I want to be proud of the way I'm living and what I stand for."
The star, who refused to use Houser's name, added: "Unless something is done and done soon, dangerous people will continue to get their hands on guns.
"We know what can happen when they do. I was heartbroken when I heard about Columbine and Sandy Hook and Aurora and so many other names of places that are seared into our memories. And I was heartbroken again when I heard about Lafayette.
"We'll never know why people choose to do these painful things, but sadly we always find out how. How the shooter got their gun. It's often something that shouldn't have happened in the first place.
"The time is now for American people to rally for these changes. These are my first public comments on the issue of gun violence, but I can promise you they will not be my last."
Schumer later appeared on US satirical news programme The Daily Show, where she said the Lafayette shooting had left her "heartbroken".
She said that, on the day of the incident, she had so many missed calls "I assumed there was a sex tape of me out or something.
"Then to hear that news, it broke my heart. It was so horrible.
"The second this happens, you want to act," she continued, and talked about joining up with her cousin to campaign for gun control.
"This has been in the works, and I was so happy he invited me to be a part of it."
Comedian Amy Schumer has called for tougher gun control laws in the US, after two women were shot dead at a screening of her movie, Trainwreck.