Supporters of expanded background checks needed 60 votes to advance their current bill, but they only got 54 votes. Forty-one Republicans and five Democrats voted to scuttle the plan.
Joined by Newtown families and former Rep. Gabby Giffords, Mr. Obama held a Rose Garden news conference to denounce the Senate action. He was introduced by Mark Barden, whose 7-year-old son was killed in the Sandy Hook Elementary School shooting.
"The fact is most of these senators could not of offer any good reason why we wouldn't want to make it harder for criminals and those with several mental illness to buy a gun," the president said. "There were no coherent arguments as to why we wouldn't do this."
Some individuals whose lives have been affected by mass shootings watched the Senate vote from the spectator galleries. After the failed vote, two of those people shouted, "Shame on you."
Vice President Joe Biden also reacted with scorn to the Senate vote.
"The United States Senate let down an awful lot of people today, including those Newtown families. I don't know how anybody who looked them in the eye could have vote the way they did today," Biden said.
The White House says 90 percent of Americans support expanding background checks for people buying guns online and at gun shows. Mr. Obama accused opponents of the measure in both parties of caving to the pressure of special interests.
"I've heard some say that blocking this step would be a victory," Mr. Obama said. "My question is: A victory for who? A victory for what? All that happened today was the preservation of the loophole that lets dangerous criminals buy guns without a background check."
The Associated Press contributed to this report.