Time may be finally running out on the filibuster, the signature dilatory tactic in the Senate embraced by some as a protector of minority rights and reviled by others as an outdated weapon of partisan obstruction.

With the announcement by Senator Kyrsten Sinema of Arizona that she will not seek re-election, the filibuster is now on track to lose the two senators who preserved it in 2022 over the objections of the rest of their party. She and her fellow filibuster defender, Senator Joe Manchin III of West Virginia, who is also retiring, left Democrats just two votes short of ending the filibuster when it came to voting law changes that were backed by a majority.

Perhaps just as significantly, Senator Mitch McConnell, the Kentucky Republican who has enthusiastically deployed the filibuster to his advantage for decades, is stepping down from his top party leadership post, reducing the influence of one of the chief practitioners and defenders of filibuster maneuvering.

Depending on how the November elections shake out, the pressure to reduce the power of the procedural tool — which effectively requires 60 votes to move any legislation forward in the Senate — could be substantial.

“It is going to be challenged,” said Mr. Manchin, who sided with Mr. McConnell and Senate Republicans to block fellow Democrats from rewriting the Senate rule book.

Senator Chuck Schumer, Democrat of New York and the majority leader, said as much recently when he suggested his party could try again to change the filibuster rules for voting rights legislation if Democrats wind up in control of the Senate, the House and the White House next year.

“When people attempt — courts or legislators — to take away voting rights, particularly of the most disenfranchised people, we have an obligation to do everything we can to restore those voting rights,” Mr. Schumer said after the decision by Ms. Sinema, now an independent, to relinquish her seat given her daunting re-election challenge.

Once rarely used, the filibuster has become a routine part of Senate life and has kept significant legislation bottled up. It was central to efforts to blockade civil rights legislation in the past but in recent years has ensnared gun control, health care and other social policy measures.

Under current Senate rules, most legislation is subject to a 60-vote threshold in order to pass. And with the two parties typically divided so narrowly, it gives the minority significant power to block measures that otherwise have majority backing.

Filibuster proponents say it is one of the defining attributes of the Senate that distinguishes it from the House, a crucial tool that forces bipartisanship and makes sure the views of the minority are heard.

“I think having to get 60 votes is a good exercise, and it makes the most extreme ideas hard to pass,” said Senator Lindsey Graham, Republican of South Carolina. “That’s a good thing.”

Its detractors say it has outlived its usefulness and essentially puts the Senate under minority rule by thwarting the will of the majority on big issues. They want to see it jettisoned, particularly given increased political polarization and the difficulty of achieving compromise in Congress.

“Americans see the dysfunction in the Senate, and the cause is directly related to the lack of majority rule,” said Senator Richard Blumenthal, Democrat of Connecticut. “All the rigmarole, the time-consuming, arcane rules that have simply been abused recently. It may have made sense at a time when people agreed to disagree and then move forward. But now people are not agreeing to anything.”

The Senate has been chipping away at the filibuster for decades, providing alternative ways to pass tax legislation, for instance, on simple majority votes — a process both parties have employed to enact economic measures. Democrats eliminated the 60-vote threshold for judicial and executive branch nominations in 2013 after they were frustrated by Republican filibusters against President Barack Obama’s appeals court nominees. Republicans later ditched the filibuster against Supreme Court nominees in 2017 to place conservative nominees on the court.

But the most significant recent attempt to gut the filibuster against legislation fell short in January 2022. Democrats, stymied on a voting rights bill that they said was needed to overcome voter suppression efforts in the states, tried to establish a new Senate precedent that would override the requirement for a supermajority vote on bills specifically related to election laws, saying such bedrock measures merited special status.

Mr. McConnell led the charge against the procedural change, warning that it would destroy the Senate. When Ms. Sinema announced her retirement, he credited her with preserving the filibuster.

“The institution of the Senate is only as strong as the people willing to defend it,” Mr. McConnell said. “History will remember that with the Senate’s defining feature under grave threat, Senator Kyrsten Sinema’s wisdom and devotion to this body rivaled that of her most seasoned colleagues.”

Mr. McConnell said repeatedly over the years that he had no intention of getting rid of the filibuster, and he resisted demands from President Donald J. Trump to jettison it to make it easier to push through conservative priorities.

With Mr. McConnell exiting leadership at the end of the year, the race is on to replace him. Both of the leading contenders, Senators John Thune of South Dakota and John Cornyn of Texas, say they are committed to keeping the filibuster alive. Mr. Thune has raised the likely possibility that a filibuster exception for voting rights, for instance, would quickly lead to exceptions for other topics, eventually eliminating the tactic altogether.

In an interview, Mr. Cornyn said he, too, was determined to keep the right to filibuster in place.

“I think the filibuster has saved the Senate from becoming the House, where purely partisan majorities can pass legislation,” he said. “I’m an institutionalist.”

But if Mr. Trump triumphs in November and Republicans hold the House and capture the Senate, the Senate leader would undoubtedly face calls to eliminate or weaken the filibuster to push through conservative legislative proposals over Democratic opposition. Those calls may be hard to resist.

In any event, lawmakers in both parties are considering the future of the filibuster with the departures of Mr. Manchin and Ms. Sinema, and with Mr. McConnell moving to the leadership sidelines.

“The handwriting is on the wall,” said Mr. Blumenthal. “It’s history.”