The longest-serving Senate leader is relinquishing his post in the next Congress and planning to use his influence in ways that could put him at odds with President-elect Donald J. Trump.

The last time President Donald J. Trump was in the White House, Senator Mitch McConnell, the Kentucky Republican who was then the majority leader, played a crucial role in empowering him and pushing through his agenda.

But Mr. McConnell, the longest-serving Senate leader, is stepping down from that post in January. This time he appears to be positioning himself to do the opposite, choosing to focus on issues that could put him at odds with Mr. Trump on policy and personnel at the dawn of his second term.

In recent days, including during a late-night session of votes on the Senate floor last week, Mr. McConnell, 82, has told colleagues that his impending exit from leadership has left him feeling “liberated.”

He has signaled skepticism about some of the president-elect’s most divisive picks for his administration, staying mum on their selections and saying last week that the withdrawal of former Representative Matt Gaetz from consideration as attorney general was “appropriate.” And Mr. McConnell has telegraphed that as he moves to cement his legacy in his remaining time in the Senate, he plans to prioritize two issues that just happen to be subjects on which he disagrees strongly with Mr. Trump.

Mr. McConnell, whose current term ends in 2027 and who has not said whether he will seek another, has said he plans to focus intently during the next two years on advancing his interventionist strain of foreign policy, which flies in the face of the president-elect’s “America First” approach. He also wants to concentrate on preserving the Senate’s institutional independence at a time when Mr. Trump, who will have a governing trifecta in January, has made clear that he means to bend the chamber to his will.

That could lead Mr. McConnell to become even more aggressive than he has previously been about pressing for the United States to back Ukraine in its fight against Russia. And people close to him have taken his recent comments to mean that he would resist any effort by Mr. Trump to use recess appointments to install cabinet and other nominees without the Senate’s approval, as well as any other attempt to co-opt the chamber.

“I think you’ll hear him speaking out more, because he has now been freed from the responsibility of speaking on behalf of the conference,” said Senator Mike Rounds, Republican of South Dakota. “He’s always been careful in the past not to put the conference in a position that other people may disagree with. But now, as simply a member again, he can speak freely for his own personal opinions. And I think he’s looking forward to that.”

Mr. McConnell has had a rocky relationship with the president-elect, who has routinely attacked the senator’s wife, Elaine Chao, Mr. Trump’s former transportation secretary. Mr. Trump has called her “Coco Chow” and suggested that she and her husband are both beholden to China.

But Mr. McConnell also has a long history of opting out of confrontations with Mr. Trump. After a violent mob of Trump supporters attacked the Capitol on Jan. 6, 2021, the senator privately flirted with voting to convict him and bar him from future office, but ultimately voted to acquit him, excoriating the president in a speech but paving the way for him to run again.

Asked at a post-election news conference at the Capitol how he anticipated working with Mr. Trump given his previous criticism of the president-elect, Mr. McConnell responded, “I will do everything I can to help the new administration be successful.”

But should he choose to break with the president, an emboldened Mr. McConnell could emerge as an influential force who provides political cover for other Republicans to resist some of Mr. Trump’s most radical and unorthodox impulses.

Late last week, Mr. McConnell outlined the clearest road map yet as to how he might try to wield influence during the next Congress, even removed from a leadership perch. He announced that he would lead two key panels: the subcommittee that controls military spending and the Rules Committee, which controls the Senate campus and gives him a perch to resist changes to how the chamber operates.

“America’s national security interests face the gravest array of threats since the Second World War,” Mr. McConnell said. “At this critical moment, a new Senate Republican majority has a responsibility to secure the future of U.S. leadership and primacy,” he continued, adding that “defending the Senate as an institution” remained “among my longest-standing priorities.”

The announcement suggested that Mr. McConnell planned to take a more aggressive footing in the Senate after stepping down as leader than even some close to him had imagined.

Privately, he has told colleagues that he is interested in mirroring the role that former Speaker Nancy Pelosi has played in shaping the Democratic Party since relinquishing the gavel in the House, according to people familiar with the comments.

“There will always be people, including me and anybody that’s got any of their own wisdom, that would lean on or at least look to Mitch for guidance on any number of things, particularly the institution and geopolitical issues,” said Senator Kevin Cramer, Republican of North Dakota. “If you don’t consult Mitch, you’re not doing everything you can do to be the best senator you can be. So he’ll always be having a role of sage. And he won’t do it passively — he will pick a few things.”

An early test will come via some of Mr. Trump’s choices for his cabinet. Even before he had announced a single pick, members of his transition team identified Mr. McConnell as a potential obstacle to their efforts to stock the highest levels of government with America First, anti-interventionist picks.

The senator has not offered public support for Pete Hegseth, the Fox News personality who is Mr. Trump’s choice for defense secretary; Robert F. Kennedy Jr., whom the president-elect wants as health secretary; or former Representative Tulsi Gabbard, the pick for intelligence chief.

Mr. McConnell has positioned himself as a leading champion of sending military aid to Ukraine and routinely criticized President Bashar al-Assad of Syria for the “butchering of his own people.” Ms. Gabbard has accused the United States and NATO of provoking the war in Ukraine and met with Mr. al-Assad.

A polio survivor, Mr. McConnell emerged during the coronavirus pandemic as a leading Republican proponent of vaccines, a stance starkly at odds with Mr. Kennedy’s worldview.

While the Senate Republican conference has become increasingly ideologically aligned with Mr. Trump in recent years, including on matters of foreign policy, its 53-seat majority will mean that a few Republican defectors could sink nominees.

When Mr. Gaetz announced last week that he would withdraw from consideration to lead the Justice Department, Mr. Trump’s most ardent supporters immediately blamed Mr. McConnell.

“You can’t take this any other way than a Mitch McConnell win,” Steve Bannon, one of the right’s most influential voices, said on “War Room,” his show. “They’re laughing up there in the Senate, they just are. They taste blood in the water.”

Republicans on Capitol Hill who know Mr. McConnell widely believe he will also resist recess appointments, should Mr. Trump force the issue.

In 2014, Mr. McConnell opposed President Barack Obama’s attempts to make recess appointments, leading an amicus brief in support of the case that led the Supreme Court to unanimously rule that Mr. Obama’s maneuvering had violated the Constitution.

When the decision came down, Mr. McConnell, speaking on the Senate floor, called it “a victory for the Senate, for the American people and for our Constitution.”

“The court reaffirmed the Senate’s clear and constitutional authority to prescribe its own rules, including the right to determine for itself when it is in session,” he said. “And the Supreme Court unanimously rejected the president’s completely unprecedented assertion of a unilateral appointment power, a power that the framers deliberately withheld from his office.”

Still, Mr. McConnell is known for sometimes changing his opinions on the bounds of permissible Senate conduct when it benefits his party. He refused to allow Mr. Obama to fill a Supreme Court vacancy several months before the presidential election in 2016 — a move that some, including Mr. Trump, believed helped his bid for the White House by placing the focus on the courts and his campaign promise to name conservative justices.

Four years later, Mr. McConnell pushed through the confirmation of Justice Amy Coney Barrett, Mr. Trump’s pick, weeks before the 2020 presidential election.