The Senate on Tuesday confirmed Betsy DeVos to lead the Department of Education by the slimmest of margins, capping off a rocky, high-stakes fight for President Trump's pick.

Vice President Pence cast the deciding vote on DeVos, breaking a 50-50 tie after Sens. Susan Collins Susan Margaret CollinsThe Hill's Campaign Report: Biden asks if public can trust vaccine from Trump ahead of Election Day | Oklahoma health officials raised red flags before Trump rally Gideon leads Collins by 12 points in Maine Senate race: poll Senate leaders quash talk of rank-and-file COVID-19 deal MORE (Maine) and Lisa Murkowski Lisa Ann MurkowskiGOP ramps up attacks on Democrats over talk of nixing filibuster OVERNIGHT ENERGY: House Democrats tee up vote on climate-focused energy bill next week | EPA reappoints controversial leader to air quality advisory committee | Coronavirus creates delay in Pentagon research for alternative to 'forever chemicals' House Democrats tee up vote on climate-focused energy bill next week MORE (Alaska) became the first Republican senators to oppose a Trump Cabinet pick, joining all Democrats.

Pence is the first vice president ever to cast a decisive vote on a Cabinet nominee. The last time a vice president broke a tie in the Senate was 2008, when then-Vice President Dick Cheney voted on tax legislation.

Pence arrived at the Capitol around approximately 11:30 a.m. but waited in the wings until the vote was tied at 50-50 to take over the presiding chair and cast his vote.

The vice president, a former lawmaker, chatted with GOP senators on the floor after the vote and shook hands with Sen. Ted Cruz Rafael (Ted) Edward CruzLoeffler calls for hearing in wake of Netflix's 'Cuties' Health care in the crosshairs with new Trump Supreme Court list 'Parks and Rec' cast members hosting special reunion to raise money for Wisconsin Democrats MORE (R-Texas).

Pence was expected to meet with Senate Republicans during their closed-door weekly policy lunch on Tuesday afternoon.

White House press secretary Sean Spicer later defended Pence making history by breaking a tie on a Cabinet nominee, calling the vote "another glaring reminder of the unprecedented obstruction Senate Democrats have engaged in throughout this process.”

Senate Minority Leader Charles Schumer Chuck SchumerDemocrats scramble on COVID-19 relief amid division, Trump surprise Pelosi, Schumer 'encouraged' by Trump call for bigger coronavirus relief package Schumer, Sanders call for Senate panel to address election security MORE (D-N.Y.) made a failed eleventh-hour plea Tuesday morning for a third Republican to buck the party and sink DeVos's nomination.

“It’s the Republican side demanding a vote for an unqualified candidate,” the Senate’s top Democrat said. “I hope against hope that another Republican will have the courage ... [to] join us.”

Schumer suggested Republicans are privately saying they wish Trump picked someone else, calling DeVos a “negative trifecta.”

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Democrats forced a rare all-night session to try to rally public support behind their opposition to DeVos’s nomination, including protesting outside of the Capitol with progressive groups.

They painted Trump’s pick as a threat to public education.

“A vote for Ms. DeVos is a vote to destroy the public school system,” Sen. Tom Udall Thomas (Tom) Stewart UdallOVERNIGHT ENERGY: House Democrats tee up vote on climate-focused energy bill next week | EPA reappoints controversial leader to air quality advisory committee | Coronavirus creates delay in Pentagon research for alternative to 'forever chemicals' Senate Democrats demand White House fire controversial head of public lands agency OVERNIGHT ENERGY: Trump extends Florida offshore drilling pause, expands it to Georgia, South Carolina | Democrats probe Park Service involvement in GOP convention | Sanders attacks 'corporate welfare' to coal industry included in relief package MORE (D-N.M.) said from the Senate floor.

Sen. Al Franken Alan (Al) Stuart FrankenPeterson faces fight of his career in deep-red Minnesota district Getting tight — the psychology of cancel culture Tina Smith wins Democratic Senate primary in Minnesota MORE (D-Minn.) added that DeVos is “fundamentally incompetent,” saying her hearing was "one of the most embarrassing scenes" he’s seen since joining the Senate.

"I believe it may have been one the most embarrassing performances by a nominee in the history of the United States Senate," he said. "We would not accept a secretary of Defense who couldn't name the branches of the military.”

DeVos, a GOP mega-donor long active on education issues, has been the subject of fierce opposition from teachers unions and other liberal groups opposed to her support for charter schools and tuition vouchers that use public funds.

And her rocky performance during a confirmation hearing was panned by both sides. At one point, she advocated for guns in school because of the possibility of a grizzly bear attack, at least in Wyoming.

But Republicans and the White House remained publicly steadfast in their support of DeVos despite a wall of opposition. They argue Democrats are obstructing Trump’s nominees because they remain bitter about Hillary Clinton Hillary Diane Rodham ClintonBarr criticizes DOJ in speech declaring all agency power 'is invested in the attorney general' Virginia Democrat blasts Trump's 'appalling' remark about COVID-19 deaths in 'blue states' The Hill's Campaign Report: Biden asks if public can trust vaccine from Trump ahead of Election Day | Oklahoma health officials raised red flags before Trump rally MORE losing the 2016 presidential race.

“We’re no longer in the midst of a contentious presidential election,” Senate Majority Leader Mitch McConnell Addison (Mitch) Mitchell McConnellSenate Republicans signal openness to working with Biden Hillicon Valley: DOJ indicts Chinese, Malaysian hackers accused of targeting over 100 organizations | GOP senators raise concerns over Oracle-TikTok deal | QAnon awareness jumps in new poll The Hill's Campaign Report: Biden asks if public can trust vaccine from Trump ahead of Election Day | Oklahoma health officials raised red flags before Trump rally MORE (R-Ky.) said. “We have a new president, and that president has put forth … a number of well-qualified Cabinet nominees.”

He added that DeVos will return power to state and local governments because she understands they are "best suited to make education decisions for our kids.”

“This is a sad day for children,” American Federation of Teachers (AFT) President Randi Weingarten said in a statement following the vote on Tuesday.

“If she wants to work with the educators who work hard every single day—in districts as diverse as McDowell County, W.Va., Detroit, and Scarsdale, N.Y.—to provide children the opportunities they deserve, we renew our invitation to have her visit America’s public schools and see the strategies that work for kids,” Weingarten said.

“But it’s more likely we’ll now hear the same trashing of public schools that the disrupters, the privatizers and the austerity hawks have used for the last two decades.”

Senate Republicans are threatening to keep the Senate in through the weekend as they try to confirm additional Cabinet nominees.

Republicans, pointing to data from the Senate Historical Office, note that the pace for confirming Trump’s picks is the slowest since George Washington. President Obama, by comparison, got seven nominees confirmed on his first day in 2009.

Senators will take up Sen. Jeff Sessions’s nomination to be attorney general on Wednesday. The move ensured the Alabama Republican was able to help bring DeVos across the finish line before leaving the Senate to take his new post.

After Sessions, lawmakers will turn to Rep. Tom Price (R-Ga.) and Steven Mnuchin, Trump’s picks to lead the Department of Health and Human Services and Treasury Department, respectively.

Democrats face an uphill battle to block any of Trump’s nominees, who only need a simple majority to clear the upper chamber. Republicans hold 52 seats, and no GOP senator has officially come out in opposition to any other Trump pick.

Schumer, however, dismissed GOP criticism, arguing Democrats had an obligation to speak out against nominees they believe are unqualified.

“We Democrats are very proud of what we have done here,” he said. “The nominee is so unqualified and the American people now know it.”

--Jordan Fabian contributed to this report, which was updated at 2:34 p.m.