In a dramatic upset that will end Democrats' super majority in the Senate, Massachusetts Republican Scott Brown defeated Democrat Martha Coakley to claim the seat held by the late Ted Kennedy for more than 46 years.
Coakley called Brown to concede the race shortly before 9:30 p.m., a Democratic aide told ABC News.
After Brown's victory was announced, the throng of supporters at his campaign headquarters chanted "John Kerry's next."
Brown, 50, a lawyer and former model, will be the 41st Republican in the Senate, meaning Democrats will no longer be able to prevent a GOP filibuster -- a major complication for President Obama's agenda and the health care legislation currently pending in Congress.
Obama called Brown to congratulate him on his victory and told him "he looks forward to working with him on the urgent economic challenges facing Massachusetts families and struggling families across our nation," White House press secretary Robert Gibbs said.
Massachusetts Secretary of State William Galvin said he would notify the Senate on Wednesday that Brown had been elected, even though he had said earlier it could take more than two weeks to certify the special election results.
That delay could have given Democrats time to try to push through final passage of Obama's health care plan.
Senate Majority Leader Harry Reid, D-Nev., said tonight that Brown would be seated "as soon as the proper paperwork has been received."
Brown has said he opposes Democrats' health care overhaul working its way through Congress, and some Democrats are even acknowledging Brown's win could imperil passage of other big ticket items, including climate change legislation, regulatory reforms and a banking industry overhaul.
Senate Majority Leader Harry Reid said tonight the loss of the 60-vote majority will not change the Democrats' priorities.
"While Senator-elect Brown's victory changes the political math in the Senate, we remain committed to strengthening our economy, creating good paying jobs and ensuring all Americans can access affordable health care," Reid said in a statement. "We hope that Scott Brown will join us in these efforts. There is much work to do to address the problems Democrats inherited last year, and we plan to move full speed ahead."
However, there has so far been little or no bipartisanship on any of the major issues Congress has faced.
Obama himself acknowledged the stakes in his stump speech for Coakley in Boston on Sunday, saying "a lot of these measures are going to rest on one vote in the U.S. Senate."
With that vote now in Republican hands, Democrats are experiencing growing concern about the future of their majorities in Congress in 2010.
"I think what's happened in the last few weeks here is a wakeup call for the Democrats both here in Massachusetts and around the country," Phil Johnston, a former chairman of the Massachusetts Democratic Party, told ABC's "Top Line" today.
Obama, who has been "both surprised and frustrated" with how hotly contested the Bay State special election became, recognizes the "tremendous amount of upset and anger" among voters about "where we are economically," White House press secretary Robert Gibbs said earlier today.
While the administration continues to deflect suggestions that the Massachusetts race may be a referendum on the Obama presidency, Republicans say the symbolism of Brown's victory is hard to deny.
"As we look forward to the midterm elections this November, Democrats nationwide should be on notice: Americans are ready to hold the party in power accountable for their irresponsible spending and out-of-touch agenda, and they're ready for real change in Washington," National Republican Campaign Committee chairman John Cornyn said after Brown's victory.
Massachusetts, where registered Democrats outnumber Republicans by more than three to one, has long been a Democratic stronghold, sending two Democratic senators to Washington for each of the past 31 years.
The last time a Republican senator was elected in Massachusetts was November 1972, when Sen. Edward Brooke won the coveted seat.
Sen. Robert Menendez, D-N.J., the chairman of the Democratic Senate Campaign Committee said the message voters sent in Brown's victory was not lost on the party.
"I have no interest in sugar coating what happened in Massachusetts," Menendez said. "There is a lot of anxiety in the country right now. Americans are understandably impatient. The truth is Democrats understand the economic anger voters feel, that's in large part why we did well in 2006 and 2008.
"In the days ahead, we will sort through the lessons of Massachusetts: the need to redouble our efforts on the economy, the need to show that our commitment to real change is as powerful as it was in 2008, and the reality that we cannot take a single thing for granted and cannot afford even a second of complacency."
Although Democrats no longer have the 60 votes needed to thwart a Republican filibuster, they still maintain the largest Senate majority either party has enjoyed since 1979 and have the ability to pass legislation through reconciliation, a process which bypasses normal Senate rules by only requiring 50 votes.
Several congressional sources say that idea is off the table for the pending health care legislation, because it would mean having to start over and could risk losing some Democratic moderates, which in turn could cost Democrats the bill altogether. But a few Democrats have suggested reconciliation is be a viable option.
House Speaker Nancy Pelosi, D-Calif., told reporters Monday, "Let's remove all doubt, we will have health care -- one way or another."
Another option: The House could pass the Senate version of the health care bill verbatim, which would send the legislation to the president's desk without protracted negotiations.
"Whether there are 59 seats in the Senate or 60, we still have to work hard to get our economy back on track. We still have to work hard to make the promise of affordable, accessible health care for millions of Americans a reality," Gibbs said earlier today.
Meanwhile, public support for the president and Democrats' plan to overhaul the health care system continues to wane.
In an ABC News/Washington Post poll released today, 51 percent of Americans said they oppose health care overhaul efforts, with only 44 percent in favor.
At its peak, in September and again in November, 30 percent of Americans "strongly" backed the proposed changes. With the plan still undergoing modifications, that has dropped to 22 percent, a new low. Substantially more, 39 percent, are "strongly" opposed, a number that's held steadier.
While special elections do not usually draw large crowds, Massachusetts election officials noted relatively high voter turnout across the state despite frigid and snowy weather in some parts of the state.
Brown's candidacy has been credited with energizing Republicans and Tea Party activists, who poured money into the state to help him campaign. A Republican source familiar with Brown's fundraising told ABC News that Brown raised more than $1 million online every day last week.
He ran what many strategists saw as a creative and spirited campaign, carefully crafting himself as a Republican.
In one ad, Brown associates himself with Democrat and former President John F. Kennedy.
Historical footage of JFK stating that money "placed in the hands of consumers and businessmen will have both immediate and permanent benefits" to the economy is followed by Brown, who adds a conservative twist, saying "every dollar released from taxation" will have a similar effect.
Brown could be sworn in as early as Jan. 29.
ABC News' Jake Tapper, Jonathan Karl, Teddy Davis and Huma Khan contributed to this report.