Vice President Mike Pence announcing the final vote, which was mostly along party lines, 51 to 49, with only one Republican voting against the bill, Senator Bob Corker of Tennessee.
The bill is the first overhaul of the tax code in 31-years.
It slashes the corporate tax rate.
And while Republicans have touted it as a victory for the middle class, several independent analyses found it's skewed toward corporations and the wealthy, according to the Tax Policy Center.
The final vote came after hours of voting on amendments to accommodate a handful of Senators' demands.
The addition that failed would have given Hillsdale College, a small Christian school in Michigan, an exemption from the new excise tax on universities.
One of Hillsdale College's notable alumni is Erik Prince, Secretary of Education Betsy Devos' brother and former Blackwater CEO who is now in the news for the Russia investigation.
Sen. Mitch McConnell / Majority Leader (R/KY) said, "Well this is a great day for the country. It's been 31 years since we've done comprehensive tax reform. We have an opportunity now to make American more competitive, to keep jobs from being shipped offshore and provide substantial relief to the middle class."
Sen. Ron Wyden (D/OR) said, "Millions of Americans must be watching in stunned disbelief tonight as the Republican Senate betrays the middle class for the benefit of faceless multi-national corporations."
The Senate bill must now be reconciled with the House version.
President Trump praised the vote on Twitter, saying he looks forward to signing the bill before Christmas.