The vote was 62 to 37.
In December, the chamber voted down a cloture motion on Aponte's nomination, 49 to 37.
Senate Majority Leader Harry Reid (D-Nev.) said he was "really happy" that the Senate ended debate on Aponte's nomination.
"She's an excellent ambassador," Reid said. "It is high time the United States has a confirmed ambassador to El Salvador, our ally."
Aponte had previously been serving as a recess appointment to El Salvador since 2010.
Sen. Robert Menendez (D-N.J.), speaking before the vote, said there had been a number of unnecessary hearings on Aponte's confirmation.
"In addition to last year's vote, the Foreign Relations Committee has held a series of meetings to confirm her nomination and, frankly, I have not seen any nominee forced to go through such an arduous and drawn-out confirmation process as Ms. Aponte," Menendez said.
The senator from New Jersey added that Aponte's qualifications should have resulted in a quick confirmation.
"As someone who personally reviewed her record, as someone who personally looked at the files, I believe there is nothing to prevent Ambassador Aponte to be confirmed by the Senate," Menendez added.
Aponte was nominated by President Obama in February 2011.
—This story was updated at 1:53 p.m.