Specter, 79, said he plans to run for re-election in 2010 as a Democrat. The move puts the Democrats closer to a 60-vote filibuster-proof majority in the Senate with important votes on health care and energy policy looming.
"Since my election in 1980, as part of the Reagan Big Tent, the Republican Party has moved far to the right," he said in a statement. "Last year, more than 200,000 Republicans in Pennsylvania changed their registration to become Democrats. I now find my political philosophy more in line with Democrats than Republicans."
Listen to Specter answer reporters' questions about his switch:
Specter emphasized his independence on matters, and said his support of the stimulus package created a schism with the Republican Party that made "our differences irreconcilable."
He was one of three GOP senators who voted in favor of the stimulus plan.
President Barack Obama called Specter almost immediately after he was informed of the decision to say the Democratic Party was "thrilled to have you," according to a White House official, quoted the Associated Press.
With Specter, the Democrats have 59 Senate seats. If Democrat Al Franken wins the contested race in Minnesota, the party would reach the 60 votes needed to approve legislation without threat of a filibuster. Franken's seat is being challenged in the courts by Republican Norm Coleman.
Franken holds a 312-vote lead over Coleman, who is asking the Minnesota Supreme Court to overturn his recount loss. Coleman contends that thousands of absentee ballots were improperly rejected. Oral arguments are scheduled for June 1.
Specter faced an extraordinarily difficult re-election challenge in his home state, having first to confront a challenge in the Republican primary before entering a general election campaign against a Democrat in a state that has trended increasingly Democratic in recent elections, reported the AP. Former Rep. Pat Toomey, whom Specter defeated in a close primary race in 2004, is expected to run again.
Specter has said in recent months that in order to win a sixth term, he would need the support of thousands of Pennsylvania Republicans who sided with Obama in last fall's presidential election.
Republicans were not given any warning of the switch. Michael Steele, chairman of the Republican National Committee, responded angrily, saying Specter "didn't leave the G.O.P. based on principles of any kind. He left to further his personal political interests because he knew that he was going to lose a Republican primary due to his left-wing voting record. Republicans look forward to beating Senator Specter in 2010, assuming the Democrats don't do it first."
Sen. Jon Kyl of Arizona, the second ranking Republican in the Senate, called the decision "a real problem."
Specter said he deeply regrets "disappointing many friends and supporters."
"I can understand their disappointment. I am also disappointed that so many in the Party I have worked for for more than four decades do not want me to be their candidate," he wrote.
Specter went on to add that his change in party affiliation "does not mean that I will be a party-line voter any more for the Democrats that I have been for the Republicans. Unlike Senator Jeffords' switch which changed party control, I will not be an automatic 60th vote for cloture. For example, my position on Employees Free Choice (Card Check) will not change."
In 2001, Sen. Jim Jeffords of Vermont left the Republican Party and become an independent, handing control of the Senate back to Democrats just as President George W. Bush began his first term.
"Whatever my party affiliation, I will continue to be guided by President Kennedy's statement that sometimes party asks too much," Specter said. "When it does, I will continue my independent voting and follow my conscience on what I think is best for Pennsylvania and America."