The 51-50 vote ends Trump's toughest confirmation battle yet. Senate Democrats debated through the night and into Tuesday morning in a last-ditch attempt to derail DeVos, buoyed by support from Republican Sens. Lisa Murkowski of Alaska and Susan Collins of Maine.
DeVos was sworn into office shortly after 6 p.m. ET. Pence administered the oath of office and said his confirmation vote earlier in the day was "the easiest vote I ever cast."
Throughout the fight, Democrats argued they needed "Just one more!" to lure away another Republican vote. But Senate Republican leaders succeeded in delivering a victory to Trump in a confirmation fight that very few expected to become as tough as it did.
DeVos' poor performance in her confirmation hearing -- punctuated by her suggestion that a school in Wyoming might want to have guns on premises to protect against grizzly bears -- contributed to roaring anger among public school supporters and teachers unions. Even before her hearing, critics pointed to DeVos's lack of experience with public schools and her bankrolling of efforts like school vouchers that could take money from public institutions.
Senate minority leader Chuck Schumer voiced his displeasure with the vote moments after she was confirmed, tweeting
, "Today @VP Mike Pence did something no one else has ever done: cast the tie breaking vote on his own cabinet nominee."
after the vote, "I appreciate the Senate's diligence & am honored to serve as @usedgov Secretary. Let's improve options & outcomes for all US students."
Sen. Chris Murphy told CNN earlier Tuesday that DeVos seemed to have no knowledge of the federal law that protects students with disabilities.
"You put those two things together, lack of compassion for what's happened to places like Sandy Hook and an inability to just understand the basic law around vulnerable students and it was clear at the end of that hearing that this was someone who shouldn't be the secretary of education," the Connecticut Democrat said.
DeVos' Senate vote comes after a dramatic 24 hours of protest from Democrats inside and outside the Capitol that lasted through the night, into Tuesday morning, with Democratic senators taking shifts in the Senate arguing against DeVos.
The delay tactics have succeeded in stalling many of Trump's most important Cabinet picks -- but Senate Republican leaders promised Monday to get votes for four nominees this week: DeVos, Health and Human Services nominee Tom Price, Treasury pick Steven Mnuchin and attorney general nominee, Sen. Jeff Sessions.
Trump himself noted this on Twitter Tuesday night.
"It is a disgrace that my full Cabinet is still not in place, the longest such delay in the history of our country. Obstruction by Democrats!" he tweeted.
Meanwhile, with each passing day, more questions have been raised about Trump's Cabinet picks. Labor Department nominee Andrew Puzder admitted Monday
to hiring an undocumented immigrant as a housekeeper.
But Senate Majority Whip John Cornyn promised to overcome Democratic tactics with long hours at the Capitol -- including the possibility of working through Saturday.
"We'll be burning the midnight oil," Cornyn said Monday.