McConnell said on Wednesday, "100% of our focus is on stopping this new administration."
His remarks cast doubt on hopes for bipartisanship and prompted renewed calls to end the filibuster.
Elizabeth Warren and Bernie Sanders were among the lawmakers to renews calls for an end to the rule.
After Senate Minority Leader Mitch McConnell said his entire focus is on stopping President Joe Biden's administration, Democratic lawmakers renewed calls to end the filibuster.
Speaking of the GOP, McConnell told reporters outside his Kentucky home on Wednesday, "100% of our focus is on stopping this new administration," NBC News reported.
"We're confronted with severe challenges from a new administration, and a narrow majority of Democrats in the House and a 50-50 Senate to turn America into a socialist country, and that's 100% of my focus," he said.
Democratic members of Congress seized on the remarks as evidence that bipartisanship was not possible, and they stressed the necessity of ending the filibuster, a rule that requires a 60-vote supermajority to pass legislation in the 100-person Senate.
"The Constitution doesn't say anything about it taking a super-majority of 60 senators to pass a bill," Sen. Elizabeth Warren tweeted. "It's time to get rid of the filibuster so Mitch McConnell doesn't get a veto over the will of the people."
Democratic Sen. Alex Padilla of California said McConnell is using "the same playbook he's used for years."
"Anyone expecting a return to some bygone era of bipartisanship isn't acknowledging the reality that we are in. We MUST eliminate the filibuster," he tweeted.
The Senate is split 50-50, with Vice President Kamala Harris as the tie-breaking vote, and some Democrats have called for the end of the filibuster as the only way for the Biden administration to accomplish its agenda. Biden himself has said the filibuster has been "abused."
"If we're going to achieve anything meaningful for working families we must use reconciliation, abolish the filibuster and pass legislation with 51 votes. We can't afford to wait," Sen. Bernie Sanders said in response to McConnell's comments.
But some moderates don't agree. Sens. Joe Manchin and Kyrsten Sinema have both refused to support the effort to abolish the filibuster, with Manchin saying it was designed to encourage bipartisan consensus, something that some progressives view as unrealistic.
"Please stop asking us about bipartisanship when this is what the leader of the other party is focused on," Rep. Ilhan Omar tweeted in response to McConnell.
"Democrats can't repeat the mistake of 2009, we must abolish the filibuster & move legislation that helps us deliver progress for the American people," she said. "Let's grow a backbone."
McConnell's statements came the same week that former Republican Rep. Justin Amash, who joined the Libertarian Party in 2019, praised progressive Democratic Rep. Alexandria Ocasio-Cortez for visiting his University of Chicago class.
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