Democratic US Senator Joe Manchin, a maverick who has often bucked party leadership in the past two years, will not seek re-election, hurting Democrats' chance of defending their thin Senate majority in the 2024 election.
"I will not be running for re-election to the United States Senate, but what I will be doing is travelling the country and speaking out to see if there is an interest in creating a movement to mobilise the middle and bring Americans together," Manchin said in a statement on Thursday.
The move by the 76-year-old lawmaker will make it very difficult for Democrats to defend his West Virginia seat.
Republicans hold the governor's office and the rest of the congressional delegation in a state that Republican Donald Trump won by a wide margin over Democrat Joe Biden in the 2020 presidential election.
Manchin earlier this year flirted publicly with leaving the Democratic Party, and appeared in July at an event with the No Labels group, where he discussed the possibility of having a third-party candidate run for president in 2024.
Polling shows dissatisfaction with the current leading White House candidates, incumbent Biden and Republican frontrunner Trump.
"We will make a decision by early 2024 about whether we will nominate a unity presidential ticket and who will be on it," No Labels said in a statement.
Manchin's departure will also raise the stakes for Democrats of several other Senate races including in Republican-leaning Montana and Ohio and highly competitive Pennsylvania and Arizona as they defend a 51-49 majority.
Democrats hold more of the seats that are up for election than do Republicans. Three seats held by Democrats are in states won by Trump in the 2020 election, while no Republican seats up for the election are in states where voters chose Biden.
West Virginia's Republican Governor, Jim Justice, has already launched a campaign for his party's nomination for Senate.
Manchin has been a key vote on every major piece of legislation of President Biden's tenure, as a moderate representing an increasingly conservative state.
His support was critical to passage of Biden's sweeping $US1 trillion ($A1.6 trillion) infrastructure law, one of the president's key domestic accomplishments.
Together with senator Kyrsten Sinema, who switched from Democrat to independent in December, Manchin has secured major concessions and scaling back of his party's legislative goals, winning him applause from conservatives and condemnations from many fellow Democrats.
The two helped protect the Senate's filibuster rule, which helped block Democrats' hopes of passing bills to protect abortion rights after the Supreme Court last year overturned the 1973 Roe v Wade decision that had established the right.
Manchin has insisted his only motivation is the coal-producing state of West Virginia and an eye on fiscal responsibility.
"I am guided by the words of my grandfather, who liked to say, 'Unmanaged debt will lead you to make cowardly decisions'," he said in a February Washington Post column.