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signature dilatory tactic in the Senate embraced by some as a protector of minority rights and reviled by others as an outdated weapon of partisan obstruction.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.