The South Carolina Republican was confirmed by a 51-49 vote, with Senate Armed Services Chairman John McCain, R-Ariz., the only Republican defector.
Mulvaney has represented South Carolina's 5th congressional district since 2011 and is expected to resign his position when he is sworn in, setting up a crowded Republican primary for his seat.
Appropriations Committee Chairman Thad Cochran of MS is grudgingly supporting Mulvaney after expressing reservations about the congressman Wednesday morning. He'd made the same statement and yet voted in favor of Mulvaney in committee.
"I will vote to oppose Congressman Mulvaney's nomination because it would be irresponsible to place the future of the defense budget in the hands of a person with such a record and judgment on national security."
"Congressman Mulvaney has spent his last six years in the House of Representatives pitting the national debt against our military", McCain said, citing several instances where Tea Party congressman from SC voted for defense budget cuts.
U.S. Sen. Lindsey Graham, R-S.C., a defense hawk, said he wasn't anxious about Mulvaney's record opposing spending increases for military operations. Mike Enzi, chairman of the Budget Committee.
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Senate gridlock over President Donald Trump's Cabinet nominees had slowed Mulvaney's path to confirmation.
Mulvaney is a co-founder of the House Freedom Caucus, a group of conservative congressmen who have pushed to shut down the federal government instead of increase the federal debt.
McCain said on the Senate floor that Mulvaney's ardent opposition to defense spending was why he couldn't support him.
"With the national debt soon to exceed $20 trillion as spending on health care, old-age entitlements, and net interest is projected to grow steeply, driving our debt to ever greater heights, it's extremely encouraging to see a fiscal conservative with a conservative track record, such as Mick Mulvaney, confirmed as director of the White House budget office", Boccia said.
Mulvaney is reportedly eyeing sharp cuts to domestic agencies such as the Environmental Protection Agency, but Trump has indicated he's not interested in tackling highly popular benefit programs like Social Security and Medicare.