Republicans argued it stigmatised the disabled
The US Senate voted to block an Obama-era regulation that strengthened gun checks on mentally ill buyers.
The measure required the Social Security Administration to report information on people with mental illness to the FBI.
Republicans argued that the rule - brought in in the wake of the Sandy Hook massacre - discriminated against the disabled, and voted it down 57 to 43.
Republican Senator Chuck Grassley, who led the repeal effort, said the regulation "unfairly stigmatises" people with mental illness and infringes on their constitutional right to bear arms.
Mr Grassley used eating and sleep disorders as examples that could fall under the regulation requiring a more extensive background check.
The regulation, however, does not stipulate that any person with a disability would be affected, instead focusing on people who are unable to deal with their own finances and require a trustee to administer them.
"If a specific individual is likely to be violent due to the nature of their mental illness, then the government should have to prove it," Mr Grassley said.
The American Civil Liberties Union and more than a dozen advocacy groups for the disabled opposed the rule, arguing it painted people with mental illness with too broad a brush.
President Donald Trump is set to approve revoking the rule, his first action on guns since taking power.
It passed the House of Representatives last week.
Democratic lawmakers also weighed in, criticising Republicans for making it easier for people with mental illness to obtain a firearm.
"I don't know why we think that somebody who literally can't manage their own financial affairs could be a responsible gun owner," Democratic Senator Chris Murphy said.
"I hope something truly awful doesn't happen because of this."
Dan Gross, president of the Brady Campaign to Prevent Gun Violence, also condemned the resolution.
"Make no mistake, this vote was really about deepening the gun industry's customer pool, at the expense of those in danger of hurting themselves or others," he said.