Senator Roy Blunt, the No. 4 Republican and a party institutionalist, announces plans to retire.

Senator Roy Blunt of Missouri, a fixture of the Republican establishment in Congress, announced Monday that he would not seek re-election in 2022, delivering a major blow to party leaders and opening the way for another conservative candidate more closely aligned with former President Donald J. Trump.

Mr. Blunt, the fourth-ranking Senate Republican who has served in the chamber since 2011, had been publicly mulling another campaign for weeks. Many Republicans had assumed he would run again after Mr. Blunt took steps in recent months to avoid alienating Mr. Trump, setting aside some of his more bipartisan tendencies.

“After 14 general election victories — three to county office, seven to the United States House of Representatives, and four statewide elections — I won’t be a candidate for re-election to the United States Senate next year,” Mr. Blunt said in a video posted on social media on Monday morning. Speaking outside of his family’s dairy barn, Mr. Blunt said he had always been interested in the “practical sense of getting the job done” but did not expound on his decision.

The departure of Mr. Blunt, 71, will accelerate a brain drain already underway among Senate Republicans. He was the rare member of Congress to serve in high-ranking posts in both House and Senate leadership, and leads Republicans on the influential Rules Committee. He was also in charge of planning President Biden’s inauguration in January, a delicate task that required him to navigate explosive political crosscurrents and the threat of violence after the Jan. 6 mob attack on the Capitol.

His decision not to seek another term follows similar ones by Senator Rob Portman of Ohio, one of Republicans’ leading policy minds and a key moderate; Senator Richard Shelby of Alabama, a deal-making former chairman of the Appropriations Committee; and Senator Patrick J. Toomey of Pennsylvania, a top party voice on free-market economic matters. Republicans are also closely watching Senator Charles E. Grassley of Iowa, 87, their longest-serving member, to see if he will seek another term.

Missouri, a one-time swing state, has shifted rightward in recent decades, meaning the seat will most likely stay in Republican hands. Mr. Blunt may well have faced a primary challenge had he run again, but there is no clear front-runner to replace him.

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