The measure mustered a 54-35 vote which fell short of the 60 votes needed to advance the legislation in the 100-member Senate.
The 35 no votes were all Republicans.
Six Republicans voted in favor of the commission.
Trump had urged Republican lawmakers to vote against it and warned of "consequences" for those who supported it.
It was the first time this year that Republicans used the 60-vote hurdle, known as a filibuster, to defeat legislation.
Republicans did not defend these positions on the Senate floor before or after the vote.
The proposal previously passed the House of Representatives with the support of all Democrats and 1 in 6 Republicans after bipartisan negotiations. »