WASHINGTON (CNN) -- In a major defeat for supporters of tougher gun laws, the U.S. Senate on Wednesday defeated a compromise plan to expand background checks on firearms sales as well as a proposal to ban some semi-automatic weapons modeled after military assault weapons.
The votes were on a series of amendments to a broad package of gun laws pushed by President Barack Obama and Democratic leaders in the aftermath of the Newtown school massacre in December.
However, fierce opposition by the powerful National Rifle Association led a backlash by conservative Republicans and some Democrats from pro-gun states that doomed some of the major proposals in the gun package.
Obama, in remarks at the White House, sharply criticized the outcome, but said the effort to toughen gun control was not over.
Supporters of stronger gun laws said the votes showed that powerful lobby groups could influence Congress to defy the wishes of the American people.
"The next time there's a mass shooting and they're asked what they did to prevent it, they're going to have to say nothing," said Erica Lafferty, the daughter of the principal of the Newtown, Connecticut, school who was killed along with 20 first-graders and five other educators in December's attack.
A statement by former Rep. Gabrielle Giffords, who was disabled by a shooting attack, and her husband, former astronaut Mark Kelly, said the Senate had "ignored the will of the American people."
Citing polls that showed around 90% support for expanded background checks, the statement said "senators voting against the measure chose "to obey the leaders of the powerful corporate gun lobby, instead of their constituents."
On the other side, the NRA's Chris Cox called the expanded background check proposal "misguided," saying it would not reduce violent crime "or keep our kids safe in their schools."
The broader gun legislation includes tougher laws on gun trafficking and straw purchases, and steps to devise ways to improve safety in schools. As originally proposed, with a provision to expand background checks, it would have been the most significant gun legislation before Congress in almost two decades.
Due to early opposition to the background check provision, Democratic Sen. Joe Manchin of West Virginia and Republican Sen. Pat Toomey of Pennsylvania worked out a compromise that was less expansive than what Obama wanted but still gained the president's support.
The Manchin-Toomey plan would have expanded background checks to buyers at gun shows and all Internet sales.
Due to procedural steps by Republican opponents, the amendment required 60 votes to pass in the 100-member chamber, meaning Democrats and their independent allies who hold 55 seats needed support from some GOP senators to push them through.
The final vote was 54 in favor to 46 opposed with four Republicans joining most Democrats in supporting the compromise. With the outcome obvious, Senate Majority Leader Harry Reid, D-Nevada, cast a "no" vote to secure the ability to bring the measure up again.
Meanwhile, four Democrats from pro-gun states voted with most Republicans in opposition.
On the proposal by Democratic Sen. Dianne Feinstein of California to update a 1994 ban on semi-automatic weapons that expired in 2004, the vote was 40-60, showing opposition by several Democrats as well as the chamber's Republican minority.
Obama had pushed for Congress to include both the expanded background checks provision and the weapons ban in any gun package. In recent weeks, he and the White House focused their efforts on winning support for the Manchin-Toomey compromise.
However, the NRA promised political retribution against supporters of tougher gun laws.
"You may not win today ... but I will say that you did the right thing," veteran GOP Sen. John McCain of Arizona said in praising Manchin and Toomey tor political courage in proposing their compromise. McCain was one of the four Republicans who supported the compromise.
Manchin earlier sounded resigned to defeat, telling his colleagues that regardless of how the chamber votes, the issue of background checks "is not going to go away."
The NRA has said an expanded background check system would be the first step toward a national gun registry and therefore a violation of the constitutional right to bear arms.
Manchin and other supporters rejected that claim, noting the compromise amendment prohibited a national gun registry and criminalizes misusing background check data for that purpose.
Reid earlier warned Republicans that the strong majority of Americans who support expanded background checks won't forget votes against the Manchin-Toomey compromise.
"The American people ... have a long, long memory," he said.
Meanwhile, an alternative package of gun proposal that reflected the NRA position also was defeated.
Offerd by conservative Republicans, the alternative plan introduced Wednesday after weeks of hearings and debate on Democratic proposals lacked any expansion of background checks but called for more funding to better enforce the existing system.
A sponsor of the Republican alternative, Sen. Ted Cruz of Texas, said it would target the gun violence problem in a way that the Democratic proposal before the Senate would not.
In response, Judiciary Committee Chairman Sen. Pat Leahy, D-Vermont, called the GOP's last-minute proposal a "weak and counterproductive alternative."
Other proposed amendments defeated Wednesday included a plan by Republican Sen. John Cornyn of Texas to make state concealed weapons permits acceptable throughout the country.
Any legislation passed would then go to the Republican-led House. So far, House Speaker John Boehner has stopped short of promising a vote on whatever the Senate sends over.
Obama and others have been highlighting daily gun violence in America in their appeal to lawmakers for stricter limits.
Many in Washington have coalesced around expanding background checks conducted on gun sales. However, settling on the exact mechanism of such a step has been difficult in a sharply divided political climate, with the NRA leading a strong lobbying effort against proposed changes.
Few amendments may pass
Polls show that a strong majority of Americans support some type of initiative to stem gun violence. In a CNN/ORC International poll released last week, 86% of Americans say they support expanded background checks.
However, a majority of Americans also fear that increased background checks would lead to a federal registry of gun owners that could allow the government to take away legally owned weapons.
White House spokesman Jay Carney called any claim that the Manchin-Toomey plan would lead to a federal gun registry and confiscation of firearms "absurd and false and wrong."
"The legislation itself prohibits that," he said, adding "what should be clear to those senators who are considering this, because it's clear to the American people, is that this is common sense."
CNN's Ed Payne, Rachel Streitfeld and Lisa Desjardins contributed to this report.