All 53 Democrats voted to support the measure, sponsored by Maryland Democrat Barbara Mikulski, but were joined by no Republicans. Maine Sen. Angus King, one of the chamber's two Independent members, broke from his usual position of caucusing with the Democrats and voted against the bill.
"This particular bill, in my view, fails to address the real causes that are driving the wage gap," King said, in a lengthy statement released after the vote Wednesday. "In addition, the bill could impose substantial burdens on businesses in justifying pay differentials."
Republicans who opposed the bill -- which has now fallen to a filibuster three times -- said the measure would mean redundant legislation that is looking to solve a problem that, legally at least, does not exist because discrimination is already outlawed under the Equal Pay Act.
But Mikulski, in a fiery statement on the Senate floor after the vote, said the Paycheck Fairness Act is necessary specifically because of where the EPA falls short on enforcement. She said employers can retaliate against women who speak to their colleagues about their salaries and when they get caught, it's just "the price of doing business."
"In many businesses, when they're caught, and the current law catches up with them, they just pay a fine and see it as the cost of doing business," she said. "Well that's not fine with us."
Mikulski slammed the "fog of filibuster" for why Congress has such a low approval rating.
"No wonder people are fed up with us, they wonder about us why when all is said and done, more gets said than gets done," she said.
Democrats say they plan to turn the wage gap, estimated as women earning between 77 and 84 cents compared to each $1 men make, into an issue in the 2014 midterm elections.
But Republicans say they aren't worried.
"When it comes to American women overall, what we've seen over the past five and a half years is less income and more poverty," said Minority Leader Mitch McConnell.
For their part, Democrats say they plan to bring up the Paycheck Fairness Act and bills like it repeatedly between now and the midterms.
"Though we lost the vote, we refuse to lose the battle. We are going to continue the fight to get equal pay for equal work," Mikulski said after the bill failed. "For the women, put your lipstick on, and let's fight on."
Celebrity Couples of 2014 [PHOTOS]