She added: “Unfortunately, I do not realistically expect the partisanship of recent years in the Senate to change over the short term. So at this stage of my tenure in public service, I have concluded that I am not prepared to commit myself to an additional six years in the Senate, which is what a fourth term would entail.”

Ms. Snowe cast key votes on bills that were dear to Democrats, including the economic stimulus measure and a law upending the “don’t ask, don’t tell” policy governing gay men and lesbians in the military. She was facing a Tea Party-backed challenger, but her opponent had failed to gain much traction in a state where Ms. Snowe was popular and had the backing of the new Republican governor.

Despite her reputation for crossing the aisle, Ms. Snowe stood firm against the health care overhaul in 2009, even though she had worked closely with Democrats on the issue for years. She complained that party leaders were ramming the measure through without offering sufficient chance to consider changes, and the experience colored her relationship with top Democrats.

Democrats in Washington immediately and gleefully cast their gaze north Tuesday, where a Maine victory that seemed unthinkable just a few hours earlier suddenly seemed possible. Representative Chellie Pingree, a Democrat widely expected to jump into the race, said in a statement, “This upcoming election is critical to the future of our working families around the country, and in the coming days I will carefully consider how I can best serve the people of Maine.” The filing date for the Maine primary is March 15, leaving new contenders little time.

Republicans said they were ready for the challenge. Senator John Cornyn of Texas, the chairman of the National Republican Senatorial Committee, said in a statement: “While I would never underestimate the fight ahead in defending any open Senate seat, Republicans remain well positioned to win back a Senate majority in November.”