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., as well as a proposal by Democratic Sen. Frank Lautenberg of New Jersey to limit the number of rounds in ammunition magazines.
Any legislation passed by the Senate 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.
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.