And when the vote ended in a tie, Vice President Mike Pence took the chair to cast a historic tie-breaking vote.
"On this vote, the Yeas are 50, the Nays are 50; the Senate being equally divided, the Vice President votes in the affirmative, and the nomination is confirmed," Pence announced.
It was the first tie-breaking vote cast by a Vice President since Dick Cheney; Joe Biden never had that opportunity during his eight years in office.
"I congratulate Betsy DeVos on her confirmation as our nation’s next Secretary of Education," said former Florida Governor Jeb Bush. "The President made an excellent choice to lead the Department of Education."
Republicans ready to move on other top Trump nominees
With the DeVos nomination out of the way, Republicans signaled they will move on to other major nominations of President Trump, moving first to the choice of Sen. Jeff Sessions (R-AL) for Attorney General.
A final vote on Sessions could come by late on Wednesday; then the Senate is expected to move on to nominations for the Department of Health and Human Services and the Treasury Department.
Here is what the rest of the week might look like: