Following Tuesday's failed motion, McConnell moved to reconsider the vote at a later date.
"We worked in good faith all year—all year long—to formulate a package that both parties could support," the GOP's McConnell said, referencing negotiations with Wyden and others.
"What we've just witnessed here is the Democratic Senate shutdown the opportunity to debate the top economic priority of the Democratic president of the United States," he added.
The Senate vote is one of a likely series of congressional hurdles to be overcome that will hinge on the support of a handful of Democrats. The White House has launched a campaign blitz directed at them in support of granting the president authority to speed trade deals through Congress.
Fast-track legislation gives lawmakers the right to set negotiating objectives but restricts them to a yes-or-no vote on trade deals such as the 12-nation Trans-Pacific Partnership, or TPP, a potential legacy-defining achievement for Obama.
McConnell, hoping to shore up support, reminded his fellow senators that Tuesday's vote simply would pave the way for debating fast-track legislation.
It "is not a vote to approve or disapprove Trade Promotion Authority," McConnell said.
He said the fast-track bill would be paired with a measure to provide training to workers who lose their jobs as a result of any trade deals. While many Republicans oppose that legislation, Democrats are demanding its inclusion.
Furthermore, McConnell said other trade measures Democrats seek could be debated as amendments to the fast-track bill.
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But Senate Democratic leader Harry Reid warned that without further trade protections being incorporated into the fast-track bill, "it's going to be very difficult to get to the guts of this, the bills we reported out of committee."
Following the failed vote, Reid said McConnell was wholly to blame for what happened, pointing to the majority leader's decision to only take up some of the bills on the matter passed by the finance committee.
The TPP would create a free trade zone covering 40 percent of the world economy—making it the biggest trade deal since the North American Free Trade Agreement liberalized trade between the United States, Canada and Mexico.
Read More TPP: What's at stake for Abe, Obama
More than two decades later, that pact is blamed by many on the left for factory closures and job losses and has soured sentiment toward the TPP.
McConnell accused senators who voted against the procedural vote of "choosing to stand with special interests."
Many in the Obama Administration contend that the TPP will be an international and domestic force for good, and help reaffirm U.S. global economic leadership. That sentiment extends to many in the Republican party as well.
"China is going around the world trying to write the rules for the global economy to benefit themselves," Rep. Paul Ryan told CNBC in April. "I don't think that's in our interest... We're either helping shape the global economy, or it's shaping us."
—Reuters contributed to this report.